Science topic

# Insulin Resistance - Science topic

Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. It can be caused by the presence of INSULIN ANTIBODIES or the abnormalities in insulin receptors (RECEPTOR, INSULIN) on target cell surfaces. It is often associated with OBESITY; DIABETIC KETOACIDOSIS; INFECTION; and certain rare conditions. (from Stedman, 25th ed)
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I was going through different ways to calculate insulin resistance, I came across the eGDR equation. It is a very good and easy reliable way to calculate insulin resistance. But, I am confused a little about how to decide the threshold for a population. also, I came across various studies where a modified version of eGDR was used, how do authors decide that they might need modified version of eGDR?
Sorry if I ask but i dont understand.
Estimated Glucose Disposal Rate (eGDR) is a measure of insulin sensitivity that is calculated using mathematical equations based on clinical and laboratory parameters. There are several modified equations available for eGDR, as researchers and clinicians have attempted to improve its accuracy and applicability for different populations.
The modifications to eGDR equations are usually based on the data from studies that show the limitations of the original equation or its applicability to certain populations. For example, some modifications may incorporate additional clinical variables such as age, gender, ethnicity, or body mass index (BMI), which have been shown to affect insulin sensitivity. Other modifications may incorporate different laboratory measures such as fasting insulin levels or HbA1c.
The threshold for eGDR varies depending on the specific modified equation used and the population being studied. Generally, a higher eGDR indicates better insulin sensitivity, while a lower eGDR indicates decreased insulin sensitivity or insulin resistance. However, the specific threshold values for eGDR may vary depending on the population studied, as different populations may have different baseline levels of insulin sensitivity and different risk factors for insulin resistance.
Ultimately, the decision on which eGDR equation and threshold to use depends on the research question or clinical context. Researchers and clinicians should choose an equation and threshold that is appropriate for their specific population and research or clinical needs.
reference :
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Type 2 diabetes is known to be due to insulin resistance, dysfunctional insulin sensitivity and impaired insulin secretion. Induction of autophagy has been reported to ameliorate type 2 diabetes complications via TFEB, mTORC1, AMPK and other pathways. Late onset autophagy was also been reported to be detrimental rather than being beneficial. I did like to know how induction of autophagy affects insulin secretion especially as it affects the beta cell biology.
As the word autophagy means eating itself which is an autoimmunity and of course affected beta cells will decrease in number and some in size and some will die (necrosis).
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How it is possible to be insulin resistant and sensitive, and at same time AN adaptations of insulin metabolism is characterised by a decrease in basal insulin levels and increase in metabolic clearance to avoid hypoglycaemia (Zuniga-Guajardo et al., 1986)?
Reference:
Zuniga-Guajardo, S., Garfinkel, P., & Zinman, B. (1986). Changes in insulin sensitivity and clearance in anorexia nervosa. Metabolism, 35(12), 1096–1100. https://doi.org/10.1016/0026-0495(86)90021-1
Anorexia nervosa is a psychiatric disorder that affects approximately 1 in 100 women in the reproductive age group. It is characterised by the inability to maintain normal weight most commonly due to intense fear of weight gain. While AN is classified as a psychiatric disorder, it often causes a range of physical consequences, such as electrolyte imbalance, amenorrhea secondary to hormonal derangements, impaired haematopoiesis, and decreased grey matter in the brain. There is a common misconception that women with active AN cannot conceive because of irregular menses or amenorrhea. In response to severely restricted energy intake, the hypothalamic-pituitary–gonadal axis (HPA) may produce hormonal secretion patterns similar to prepubertal or early pubertal individuals. Luteinising hormone pulses in women with AN tend to have low pulse amplitude in general, which can result in amenorrhea. AN has a fluctuating course of illness with periods of partial recovery and deterioration. Some women with AN have irregular periods rather than amenorrhoea.
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The literature indicates that yoghurt contains live bacteria that have major effects on gut dysbiosis, metabolism, insulin resistance and neurodegeneration. Gram negative bacteria release bacterial lipopolysaccharides (LPS) that have critical effects on insulin resistance and amyloid beta aggregation with relevance to diabetes and Alzheimer’s disease. The use of yoghurt, cheese and milk should be used to reduce gram negative bacteria and reduce plasma LPS levels that are markedly elevated in the developing and third world individuals.
RELEVANT REFERENCES:
1. Le Roy CI, Kurilshikov A, Leeming ER, et al. Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome [published correction appears in BMC Microbiol. 2022 Feb 28;22(1):66]. BMC Microbiol. 2022;22(1):39.
2. Lisko DJ, Johnston GP, Johnston CG. Effects of Dietary Yogurt on the Healthy Human Gastrointestinal (GI) Microbiome. Microorganisms. 2017;5(1):6.
3. Aslam H, Marx W, Rocks T, et al. The effects of dairy and dairy derivatives on the gut microbiota: a systematic literature review. Gut Microbes. 2020;12(1):1799533.
4. Le Roy, C.I., Kurilshikov, A., Leeming, E.R. et al. Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome. BMC Microbiol 22, 39 (2022).
5. V Yu Kontareva et al. Yogurt enriched to correct intestinal microflora in dysbiosis. 2020 IOP Conf. Ser.: Earth Environ. Sci. 548 082051.
6. Suzuki Y, Ikeda K, Sakuma K, Kawai S, Sawaki K, Asahara T, Takahashi T, Tsuji H, Nomoto K, Nagpal R, Wang C, Nagata S, Yamashiro Y. Association between Yogurt Consumption and Intestinal Microbiota in Healthy Young Adults Differs by Host Gender. Front Microbiol. 2017 May 11;8:847.
7. LPS Regulates Apolipoprotein E and Aβ Interactions with Effects on Acute Phase Proteins and Amyloidosis. Advances in Aging Research 03/2015; 4(2):69-77.
8. Unhealthy Diets Determine Benign or Toxic Amyloid Beta States and Promote Brain Amyloid Beta Aggregation. Austin J Clin Neurol 2015;2(7): 1060-66.
9. Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases. Int J Mol Sci. 2015;16(12): 29554–29573.
10. The Role of Clinical Proteomics, Lipidomics, and Genomics in the Diagnosis of Alzheimer’s Disease. Proteomes, 2016. 4(2) 1-19.
11. Food quality induces a miscible disease with relevance to Alzheimer’s disease and Neurological diseases, J Food Research, vol. 5, pp.45-52, 2016.
12. Bacterial Lipopolysaccharides Change Membrane Fluidity with Relevance to Phospholipid and Amyloid Beta Dynamics in Alzheimer’s Disease. J Microb Biochem Technol. 2016; 8: 322-324.
13. The Future of Genomic Medicine Involves the Maintenance of Sirtuin 1 in Global Populations. Int J Mol Biol . 2017. 2(1): 00013.
14. Bacterial Lipopolysaccharides and Neuron Toxicity in Neurodegenerative Diseases. Neurology Research and Surgery. 2018; 1(1): 1-3.
I believe the following reference is highly relevant:
German JB, Dillard CJ. Saturated fats: A perspective from lactation and milk composition. Lipids 2010; 45 (10): 915-23.
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Diabetes is a multifactorial disease characterised by chronic hyperglycemia as the baseline symptom. However, specific dietary components have been implicated as classic independent risk factors. Scientific investigations of these on-switches with respect to the pathogenesis of types I and II diabetes is very vital in preventive clinical practice. What is the distinguished "nutritional sword of Damocles" that usually precipitate insulin deficiency/pancreatic beta cell destruction as well as insulin resistance? How do these dietary agents instigate molecular cascades to initiate and also sustain lifelong hyperglycemia?
Type 1 Diabetes Mellitus is almost purely genetic but type DM pathogenesis is involved considerably with diet related almost all excessive carbohydrates taken by the person.
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Hi,
I am interested in creating insulin-resistant 3T3-L1 adipocytes using TNF-alpha, and I have the following questions:
1. Would it be best to use human TNF-alpha or mouse TNF-alpha?
2. What is an appropriate buffer to prepare the stock solution of TNF-alpha?
3. If I aliquot and freeze the solution, how long can I keep it in -20C. And for an aliquot that I thaw and dilute, how long can it stay in a 4C fridge?
4. For testing glucose uptake, can I use an indirect glucose assay (measuring how much glucose is left in the medium)? Or would you recommend using 2-NBDG?
Thank you very much
Hi Nawaz Khan , based on my experiment, i found the insulin concetration is important in inducing adipogenesis. I firstly used 1 ug/ml insulin in induced-medium, the result is not good. Then I tried 10ug/ml insulin (the concentrations of IBMX and DEX are the same as yours), the adipogenesis is visible to naked eyes after 48 hours, but the cells' ability of adhering is weakened, so i treated them very very tenderly. Some researchers recomand 1-10ug/ml insulin. Maybe you can try higher insulin concentration, like 5 ug/ml or 10ug/ml. Wish you luck~
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One of mode for treating type-2 diabetes is insulin injection. As per the pathophysiology there is insulin resistance to insulin for extra-hepatic tissues resulting in hyperglycemia. Does insulin is given very high amount in comparison to physiological levels which are unable to activate GLUT-4?
Insulin resistance is a feature of type 2 diabetes, and it can be present with prediabetes. Insulin is essential for enabling the body to use glucose effectively and prevent blood sugar levels from rising too high. When insulin does not work effectively, blood sugar levels can rise, and diabetes can develop.
Treatment with insulin and other drugs: – Daily insulin injections or using an insulin ...
Lifestyle treatments: – follow a treatment plan and medical advice; – follow an active, ...
Insulin resistance: Causes, symptoms, and prevention
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Hi, somebody knows about insulin resistance mechanisms of tobacco? I would like to begin a research project. I have some ideas but I would like to read you all.
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In the literature reviewed, there are several ways to determine insulin resistence, the best known being the HOMA index.
best index been homeostasis model assessment of insulin resistance (HOMA-IR)
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During pregnancy, maternal tissues become increasingly insensitive to insulin.
What is the best treatment for insulin resistance in a pregnant woman?
Less physical activity may be more important than excessive eating for the development of insulin resistance in human body
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Experts in the field of metabolism, what is the appropriate fasting period prior to investigating intraperitoneal Glucose or Insulin sensitivity test? This publication: https://nature.com/articles/s42255-021-00455-y suggested 2 hours while this: https://nature.com/articles/s42255-021-00414-7 recommended 6 hours.
Hello.
For Glucose sensitivity test and start the test first hour in the morning, after overnight fasting. For the Insulin sensitivity test we withdraw the food at the first hour in the morning and start the test one hour later.
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Does creatine supplementation increase insulin sensitivity?
What is your opinion?
Evidence:
"Acute Cr supplementation (20 g.d(-1) for 5 d) followed by short-term Cr supplementation (3 g.d(-1) for 28 d) did not alter insulin action in healthy, active untrained men"
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I have a few articles that are examining the factors of insulin resistance amongst Type 2 DM patients. These articles are cross sectional studies that uses questionnaires and surveys in their study. The researchers did not conduct any face-to-face interview or lived experiences. Thus, to appraise these articles, I used the JBI critical appraisal for Analytic Cross-Sectional Studies. Am I on the right track?
The JBI checklist is the most popular of these three tools. Typically, a descriptive cross-sectional research is done to determine illness prevalence and incidence. As a result, the critical appraisal instrument for analytic cross-sectional study is inappropriate for the evaluation.
The goal of this assessment is to evaluate a research's methodological quality and to identify how well a study handled the risk of bias in its design, conduct, and analysis.
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I know there have been so many rodent animal models of type 2 diabetes, but their hyperglycemia mechanisms are various (e.g. insulin resistance, beta cell destruction). Is there any suitable model for us to evaluate the GSIS function only of pancreatic beta cells? What I want is that, when I evaluate the GSIS function of pancreatic beta cells, other factors such as ER stress, beta cell apoptosis, and insulin resistance are no need to be considered.
You can feed them with a high fat diet until they are diabetic. Animal feed producers can make the special food upon request.
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Hi
I am working on hepatic insulin resistance and currently looking for any accurate and cost effective ways to measure the glucose uptake within the cells and in the media. Can anyone suggest me an appropriate assay along with its detailed procedure.
Thank you
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What is the recommended dose of insulin to perform insulin tolerance test in C57BL/6JUnib mice (fed on chow or high-fat diet)? I have found 0.1 to 10 UI/kg in the literature. Which is an adequate fasting time?
Dear Natalia,
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is anyone looking to be able to measure glycated insulin? Glycation (sometimes incorrectly called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives.
Most monosaccharides, including glucose, galactose and fructose, spontaneously bond with hemoglobin, [hgAc1]when present in the bloodstream of humans. Glycohemoglobin, hemoglobin A1c provides a three (3) month average of fasting glucose levels.
My hypothesis is the glycation of insulin is mainly responsible for cell's resistance to insulin
Is there a standardized laboratory test for glycated insulin?
It is an interesting question but I have not heard of such test. If it dives indication of Insulin resistance, then it would be useful.
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I want to know what are the different cell lines available for Polycystic ovary syndrome. What cell lines can be best used to understand insulin resistance in PCOS?
@Amos Thank you for the information
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I plan to treat C57BL/6J mice with a Western-type high-fat, high sugar diet for 16 weeks to induce obesity and NAFLD. I also plan to study ex-vivo central insulin resistance (Western blot in the hypothalamus). Doses of insulin range from 0.5 - 1 U/Kg BW to 5 U/mice in the published papers. I would appreciate receiving an expert opinion about the recommended insulin dose to be injected before sacrifice.
We would use a 3U/Kg i.p. dose of insulin in fasted animals (5hrs as overnight fasting is very stressful for mice). Tissue is harvested 15 mins post injection.
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the aim is to induce insulin resistance.
Hi Pourya,
Do you change the fructose solution, at least once, but preferably twice a week? I feed my mice a 32% fructose solution (D-fructose diluted in tap water and sterile filtered) and I find they have no problem drinking it, but you have to change the solution and the bottles regularly as two things can happen: the solution dries in the spout and blocks it, or that the solution starts to smell bad - the solution has a high concentration of sugar so it shouldn't get contaminated, but I have noticed the smell changes.
Hope this helps!
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The aim is to induce insulin resistance in male wistar rats weighted 200-300 grams, fed with normal chow
As mentioned, it could be palatability. However, you could also use special HFD or HFHS diets to induce insulin resistance in your rats.
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TFAs take on similar properties as saturated fats, and appear to be more atherogenic. High intakes of saturated fats may promote insulin resistance. Since elaidic acid (EA), the trans isomer of OA, can be found in hydrogenated cooking oils and fried foods. We aim to assess the effect of this trans fatty acid (EA) on animal model by inducing diabetes using different doses.
TFA intake is directly associated with the development of diabetes mellitus (DM) remains unknown.
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I'm trying to understand the causal mechanisms for Type 2 diabetes and would like to know the sufficient and necessary factors for type 2 diabetes.
Some genetic factors
Lipolysis in the consequence of basal insulin defiency
(Keto-)Acidosis,
Some hormones (like growth hormone and others)
Some drugs, mostly hormones itself (e. g. cortisone)
Insulinreceptor-Down-regulation
Antibodies against insulin and its receptor
Liver cirrhosis
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Most causes of type 2 DM are secondary such as insulin function, insulin resistance, obesity, recycling of the receptors, GlucT4 trafficking, etc, even genetics impact depend on epigentics factors that includes, lifestyle, nutritional etc.
Thank you, agreed with Mitchell V Kaminski , but it is not universal, some people never develop diabetes despite doing the same (overconsumption of refined sugar). Where is the defect that brought some to suffer from diabetes while the same is not observed in their counterparts?
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I want to apply regression analysis using SPSS. Kindly help as to how to apply the regression model in the study where i have recorded Weight, BMI, Total body fat mass, insulin resistance and nerve conduction velocity in type 2 diabetics.
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To establish insulin resistance, should HOMA-IR or the triglyceride glucose index (TyG) be used?
The TyG index was evaluated as a surrogate method for estimation of insulin resistance and it proved to perform better than HOMA in recent research
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In this case-control study, 60 patients with in vitro fertilization (IVF)/intracytoplas- mic sperm injection (ICSI) indication were subdivided into 3 groups as follow: 20 subjects were assigned to control (fertile women with male infertility history) group, 20 subjects with PCOS were insulin resistant (IR) and 20 subjects with PCOS were insulin sensitive (IS). After puncture, retrieved oocytes were classified into metaphase II (MII) as mature and in metaphase I (MI) or germinal vesicle stage (GV) as immature. Regres- sion analyses were used to explore the association between MII oocyte number and demographic and clinical variables. LH/FSH ratio was significantly higher in PCOS-IR women compared to controls but not significantly dif- ferent from that of PCOS-IS group. PCOS-IR women had lower MII oocyte number compared with that of controls. According to multiple regression analysis, the number of previous assisted reproductive technology (ART) cycles was negatively associated with the number of MII oocy
From this possibility you can influence the amount of M2
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Treating children known to have metabolic disorders often includes ensuring adequate amount of calories for age and weight to avoid catabolism, that is usually by giving glucose solution 10%.
What is the long term impact of the sugary fluids on these patients?
Does it contribute to generating some degree of insulin resistance?
Can we predict the insulin resistance if so?
will HOMA-IR serve as a good predictor test?
Perhaps the “ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: Carbohydrates” and related publications provide the appropriate and practical instructions for glucose infusion in children [1]. Excessive chronic glucose infusion may lead to hyperglycemia, which leads to increased lipogenesis and adipocyte fat deposition along with subsequent hepatic steatosis, elevated hepatic VLDL triglycerides, hypercholesterolemia, and may ultimately cause insulin resistance (IR) [1]. The magnitude of this effect depends individually and is affected by pre-existing metabolic stress or disease [1]. The gold standard for determining IR is the euglycemic–hyperinsulinemic clamp technique [3]. This method is considered invasive, costly, and impractical for large samples. Despite its modest specificity and sensitivity, HOMA-IR is used as an IR surrogate and alternative index in a large number of studies, including those dealing with children [4]. Other IR indexes with varied specificity and sensitivity, as well as purposes, are available [3,4].
References:
[1] Mesotten D, Joosten K, Kempen A, et al. ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: carbohydrates. Clinical Nutrition, 2018; xxx: 1-7. http://dx.doi.org/10.1016/ j.clnu.2018.06.947.
[2] Sanchez-Garc´ıa A, Rodr´ıguez-Gutierrez R, Mancillas-Adame L. et al. Diagnostic accuracy of the triglyceride and glucose index for insulin resistance: a systematic review. International Journal of Endocrinology, 2020; ID 4678526, 7 pages. https://doi.org/10.1155/2020/ 4678526.
[3] van der Aa Marloes P, Catherijne AJK, Anthonius dB, et al. Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus. Journal of Pediatric Endocrinology and Metabolism, 2017; 30(2):123-131.doi:10.1515/jpem-2016-0242.
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A study by Peeters et al. (2017) suggests that sugar traps cancer in a 'vicious cycle' which make it more aggressive and harder to treat (1). On the question-and-answer site Quora, Ray Schilling, MD, concludes: "there is a connection between the consumption of sugar and starchy foods and various cancers in man. Animal experiments are useful in suggesting these connections, but many clinical trials including the Women’s Health Initiative have shown that these findings are also true in humans. It is insulin resistance due to sugar and starch overconsumption that is causing cancer" (2).
References
1. Peeters K, Van Leemputte F, Fischer B, Bonini BM, Quezada H, Tsytlonok M, Haesen D, Vanthienen W, Bernardes N, Gonzalez-Blas CB, Janssens V, Tompa P, Versées W, Thevelein JM. Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras. Nat Commun 2017; 8: 922. doi: 10.1038/s41467-017-01019-z. https://www.nature.com/articles/s41467-017-01019-z.pdf
2. Schilling R. Why isn't sugar portrayed as bad like cigarettes? https://www.quora.com/Why-isnt-sugar-portrayed-as-bad-like-cigarettes
The fact that cancer cells use more sugar than non-cancer cells, known as the Warburg effect, appears to form the basis of the current question. Nevertheless, it is not yet known if this effect is merely a symptom of cancer or whether it is the cause of cells becoming cancerous. Evidence indicating the way cancer cells metabolize sugar is not conclusive, either. Considering refined or added sugar, the bulk of the available evidence indicates that sugar is not a carcinogen. There is no evidence that eating sugar causes cancer or speeds up its growth. There is also no evidence that eliminating dietary sugar causes cancer to shrink or disappear. However, it is known that eating excess sugar, especially added sugars, can contribute to many chronic diseases such as obesity and diabetes, which are potential risk factors for several types of cancer.
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We knew from research that chromium is essential element to millions of peoples,
Chromium is an essential mineral that appears to have a beneficial role in the regulation of insulin action, metabolic syndrome, and cardiovascular disease. There is growing evidence that chromium may facilitate insulin signaling and chromium supplementation therefore may improve systemic insulin sensitivity. Tissue chromium levels of subjects with diabetes are lower than those of normal control subjects, and a correlation exists between low circulating levels of chromium and the incidence of type 2 diabetes. Controversy still exists as to the need for chromium supplementation. However, supplementation with chromium picolinate, a stable and highly bioavailable form of chromium, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Since chromium supplementation is a safe treatment, further research is necessary to resolve the confounding data. The existing data suggest to concentrate future studies on certain forms as chromium picolinate and doses as at least 200 mcg per day.so why we dont take chromium tablets?
Chromium picolinate, specifically, has been shown to reduce insulin resistance . Chromium levels decrease with age. Studies show that people with type 2 diabetes have lower blood levels of chromium than those without the disease
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Vitamin-D plays role in maintaining insulin secretion from pancreatic beta cells. Vitamin-D deficiency contributes to the development of insulin resistance and onset of diabetes. Does vitamin-D supplementation in deficient patients prevent the development of diabetes? If so, what will be the minimum daily/weekly amount to be supplemented?
An observational study from the Nurses Health Study51 that included 83,779 women > 20 years of age found an increased risk of type 2 diabetes in those with low vitamin D status. A combined daily intake of > 800 IU of vitamin D and 1,000 mg of calcium reduced the risk of type 2 diabetes by 33%
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Dear Researchers,
I am planning antidiabetic study laboratory study using Wistar albino rats. Aim of the study is to evaluate antidiabetic potential, quality of life, herb-herb, herb-drug interaction of two polyherbal formulations present in the local market and metformin will be standard. We plan to study liver, kidney, heart, pancrea protection by these formaltions in addition to antihyperglycemic, antihyperlipidemic effect and effect on oxidative stress. OGTT will be performed before and after the study.
Need advise - should we perform insulin sensitivity and insulin resistance, both test in preclinical diabetic studies?
Dear Vishnu, I usually always perform both ITT and OGTT, you can add IPGTT if you are trying to assess the role of incretins. Some of your animals may be insulin resistant only or glucose intolerant only, having the two tests is essential to clearly monitor what is the physiopathology. Plus, unlike mice, Wistar are outbred rats that will result in higher variability among the animals.
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Hi,
I am not sure whats the best way to "control" for pubertal stage and gender in my analysis.
Actually, puberty is classified in 5 stages (1=prepubertal to 5=fully grown). To make it easier and also get more or less two groups with the same size, I also classified them into 1=prepubertal and 2=pubertal(stages2-5), which is valid from a clinical perspective.
So, what I want to do:
I want to see how continous marker X correlates with Insulin resistance (continous) AND if continous marker X is able to predict insulin resistance.
However, I am a bit stuck how to best implement pubertal status and gender in this analysis. it is likely that pubertal stage is somehow a confounding factor (since it is associated with insulin resistance), and maybe also gender.
--> How do I solve this? do a partial correlation with gender and puberty as cofactors? add them as first independent variables in a logistic regression model? how do I see/can say that puberty really influences the relation between marker X and insulin resistance?
If puberty is a confounder, it would then be possible to do two subgroup-analysis seperately evaluating the marker in prepubertal and pubertal children. (?)
Ziegelasch, N., Vogel, M., Müller, E. et al. Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage. Pediatr Nephrol 34, 449–457 (2019). https://doi.org/10.1007/s00467-018-4087-z
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Hi,
I have completed a study collecting demographics, sleep data and measures of glucose homeostasis in older adults. I have fasting glucose, fasting insulin and Hba1c for each participant. I wanted to use HOMA-IR as a measure of insulin resistance in the population but I am struggling to find consensus regarding HOMA-IR cut-offs. Ethnicity and race seem to have a significant effect. My population is based in Australia (however I would expect have mixed heritage though I did not collect that data). Any advice on what HOMA-IR cutoff would be acceptable and any literature to support same?
Thanks,
Aisling
Dear colleague,
there are unfortunately no cutoff value. My suggestion, whatever the aim of you work is, is to provide quartiles or quintiles of HOMA-IR in your descriptive statistics. This is the most widely used methods when discussing HOMA index.
If you need a cutoff for any kind of binary statistics, the most reliable paper would probably be the one from Ascaso and colleagues (Diabetes Care 26:3320–3325, 2003).
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Happy new year researchers! I was wondering if you knew of any reported cases of Medullary thyroid Ca in patients on Liraglutide (a GLP-1 agonist that's used for diabetes, insulin resistance, as well as help with weight loss). There is a theoretical increased risk of Medullary thyroid Ca in patients with a history of MEN2 (study was done in rats I believe), but I couldn't see any in human studies. We have been using this drug more in our practice due to the increased rate of diabetes and obesity in general in our patient population and not all patients are able to provide a dependable family history.
Thank you!
HV
Interesting question. Rodent studies have indeed showed dose dependent increase of calcitonin in clinically relevant doses. However, the relevance of rodent models with humans is unknown. Long term epidemiological studies will be needed in order to have a reliable answer. In the meantime, FDA recommends avoidance of use of these drugs in patients diagnosed with medullary thyroid cancer, patients with familial history of medullary cancer, or MEN2. Indeed, it is difficult to have a reliable family history on syndromes of multiple endocrine neoplasms. In the meantime, FDA recommends calcitonin measurement and thyroid ultrasound in patients treated with GLP1 receptor agonists. There are also a few case reports of people that were diagnosed with medullary thyroid carcinoma while being on GLP1 receptor agonist treatment. However, it is not straightforward to prove causality. Registries of patients with medullary thyroid carcinoma will be helpful in providing an answer. In rodents, the development of medullary thyroid carcinoma had a significant latency, about 25% of rodent life time was needed for the diagnosis of medullary carcinoma. Thus, pharmacovigilance is needed and careful consideration before prescription of GLP1 receptor agonists in children.
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I was wondering whether high-fat diet or high-sugar-high-fat diets are more commonly used for diet induced obesity in rodents?  And the reasoning behind using one or the other.
When i do a pub-med search i see more hits for 'high-fat diet' for rodents, although there are many different terms for a high-sugar-high fat diet, so its hard to say.  I would have expected that HFHS would be more effective.
I'm interested in which is the most effective at inducing obesity, and in particular i'm interested in the effect of the quality of the diet on inducing overeating behaviour.  (i'm not planning on conducting experiments, rather looking at the findings in the literature).    In general, I'm hoping to get impressions of 'experts in the field' as to what researchers generally use and why...
Hi,
always used only high-fat diet, or high- proten or high -fiber ,according to experimental models from previous studies. But usually we use one or the other.
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In the clinical world, GLP1 agonists and SGLT2 inhibitors are not commonly co-prescribed, though given the benefit of weight loss, cardiovascular benefits, and blood glucose control in patients with insulin resistance as well as obesity, should this be more commonly used? Thank you!
Thank you!
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As per available records, PCOD develops due to imbalance of the two female hormones (estrogen and progesterone) where estrogen taking the upper hand.
Common symptoms are:
1. Menstrual irregularities,
2. Infertility,
3. Increased risk of Endometrial (inner lining of the uterus) cancer,
4. Increased risk of Breast cancer,
5. Insulin resistance,
6. Obesity and increase in weight (mainly around the waist),
7. Unwanted excess hair growth on face and body,
8. Acne
9. Dark pigmentation of skin around the neck etc.
BUT
What are the actual reasons works behind development of that dangerous disease?
Is it curable?
How can it be prevented?
Polycystic ovarian disease (PCOD) is widely dependent on genetic, environmental, lifestyle and ethnicity factors including body weight. Weight loss improves the endocrine profile and increases chances of ovulation and pregnancy.
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Adiponectin as a drug
Hi Laith,
you must see this paper from DiabetesCare (https://care.diabetesjournals.org/content/26/8/2442) to see its role on IR/IS. It is well known to be measured in human as a markers for metabolic syndromes but even though it could be interesting to use it to overcome such diseases, since adiponectin can have other roles in cells (as anti-inflammatory effects, reproduction changes, cancer onset...), lifetime changes should produce more risky results (nutrition, sports...) than use of hormones.
fred
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Diabetics is attacking millions in the universe, magnesium deficiency has been linked to insulin resistance, which is central to the development of type 2 diabetes, research shows. On the flip side, increasing your intake of magnesium has been shown to possibly lower your risk of developing the chronic disease. Research suggests consuming 100 milligrams (mg) of magnesium through eating foods rich in the mineral may decrease the risk of diabetes by 15 percent. Researchers noted more study would be needed before recommending a magnesium supplement to prevent diabetes.
Not as many studies have looked into the relationship between type 2 diabetes and magnesium once you have already been diagnosed, though one study published in August 2015 in the World Journal of Diabetes noted that people with the disease who are deficient in magnesium may be more likely to have complications, such as issues with heart health. According to the Centers for Disease Control and Prevention (CDC), people with diabetes are about twice as likely to die of heart disease as people without diabetes.,but now what is link between diabetic and magnesium?
Diabetes is frequently associated with magnesium (Mg) deficit.
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hello everybody,
I would like to measure Hepatic insulin sensitivity both in vivo and cultured cells. Thus, I am looking for new methods other than traditional previous approaches such as (glucose clamp, IPGTT, IPITT, radiolabeled 2-deoxyglucose).
Your cooperation is highly appreciated.
Best regards,
Faheem
HOMA is the best method to calculate insulin resistance.
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I'm asking for the most common PAI-1 gene polymorphism related to metabolic syndrome or any of its Pillars ( diabetes - obesity - insulin resistance ).
i need RS and the primer.
Hi Mohamed
I think you're searching for this paper ( ) and related ones.
fred
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Fructose is found in many processed foods and beverages
There are putative mechanisms for Insulin resistance, induced by fructose
eg https://www.mdpi.com/2072-6643/9/3/230 see diagram from article
Its association with complications of insulin resistance, eg NAFLD [fatty liver] and the potential magnitude of its health effect on populations should point us to regulating its usage.
Should we be doing more to control the use of fructose: is there enough evidence?
There are existing data on the metabolic and endocrine effects of dietary fructose that suggest that increased consumption of fructose may be detrimental in terms of body weight and adiposity and the metabolic indexes associated with the insulin resistance syndrome,
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So, let's say some subject body presented these characteristics:
• β-cell life-span increased (SOD, Cat, GSH-Px expression increased, no abnormalities with them afterwards)
• β-cell insulin secretion increased (increased cell signals)
• GLUT4 expression increased and thus, achieving cell insulin resistance reduction (I have written GLUT2 before, but it was a typo)
• All of the above bringing the blood glucose to somewhere between 60 - 99 mg/dL (2 hours or so, after meal)
Given the subject is a T2DM affected, if the above could be achieved, can the subject be considered as cured?
Prince Nkemakolam Okoroh yes, you're right... but what if this scenario could be maintained without further treatment, would it mean that the treatment worked and the person is now free of T2DM?
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Insulin resistance, endocrine
Thanks Zainab
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It is easy to find references about diabetic-hypertensive animal models, but hard to find some infomation about the cell model. In addition, I may focus on type 2 diabetes with insulin resistance more than other types of diabetes.
I've find a phD dissertation named In Vitro Diabetic-Hypertensive Cellular-Response Evaluation Model for In-Stent Restenosis, which used FlexCell-3000TM system (Flexcell International, NC) and a peristaltic pump (Cole-Parmer) to help building the cell model. Since my lab doesn't have these machine, I would like to know whether there are other useful methods. Any idea about this topic is welcome. :)
I would suggest you ask Prof. Melvin Hayden. He is a participant on Researchgate. Good luck!
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Hello there, genotype matters is not something I know much about, so I decided ask about my situation here hoping that I could get some insights.
I am working on some immune receptor and I am using 2 KO strains; one obtained by CRISPR and the other one is more traditional ES mice. Apart from that, the strain (C57), diet, age, gender, housing... Everything is the same! Interestingly, these 2 KO mice show different metabolic phenotype. One put more body weight, more insulin resistance, etc. than other counterpart.
I am really confused what might be the reason to that. Is it do you think some changes by the CRISPR off-target effects?
I am talking to a sequencing service. Maybe I will send some samples for whole-genome sequencing, but it is pretty expensive. Do you think how many mice do I need to sequence for a healthy comparison? 1 from each enough? Or is there any other way you could suggest apart from sequencing?
I appreciate any comment, thank you very much.
Hi Fahrettin,
What you are describing is relatively common. I recommend you look for your gene at http://www.mousephenotype.org/ to see if other knockouts have been subjected to systematic phenotyping by the IMPC.
If what you say is correct (both are pure C57Bl/6 background), there can be many explanations including CRISPR off-target effects. Try looking at flanking genes to see if it would make sense that introducing genetic elements might have disturbed transcription factor binding sites, then check the expression of those genes by qPCR. It's good also to look carefully at the targeting strategies to be sure that they will be complete knockouts and that all mRNA variants will be affected including those with alternative start codons.
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Why is polycystic ovary syndrome (PCOS) rising all over the world?
PCOS is heavily linked to insulin resistance. With the rise of non-communicable diseases globally including type 2 diabetes and metabolic syndrome, the incidence of PCOS is expected to also increase considerably.
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The role of hyperglycemia, saturated fatty acids, oxidative stress, inflammatory cytokines have been investigated in causing insulin resistance. However, is hyperinsulinemia itself not likely to cause insulin resistance as a negative feedback mechanism?
A very interesting exchange. I refer you all to a new review i had written on how hyper-insulinemia can cause insulin resistance (Najjar and Perdomo, Physiology, May issue-2019).
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Are all patients with congenital generalized lipodystrophy suffer from insulin resistance or it is a consequence that could happen later in the course of the disease?
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Previously there has been evidence to suggest an inflammatory response to endotoxaemia inhibiting the insulin signalling cascade. Is there any new evidence either way supporting or conflicting this potential metabolic effect through the gut?
Great question. While certainly a key player in macrophage recruitment to adipose tissue and subsequent inflammation, I would just like to point out that there is certainly conflicting evidence as to whether LPS is required for the systemic glucose/insulin intolerance that we observe with endotoxemia. Have a look at this 2012 paper which used a model of reduced LPS-immunogenicity for comparison.
Although, I'm sure others may be able to contribute something more recent in the literature.
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I am having problems with my animals, because they aren't insulin resistance.
I started giving HFD 60% (54% land and 6% oil) for them with 6 week old and with 12 weeks of HFD they are not insulin resistance. I'm using C57Bl/6J mice and I have already found many articles in literature that use this model and they become insulin resistance, in some cases with 8 weeks of high-fat feeding.
What could be happening? I'm really woried, because they need to be insulin resistance for me to start the treatment with a ligand!!
Hi Maiara,
ITT protocols vary, but as rule mice need to fast before insulin injection, in order to bring mice to a similar level of blood glucose, because you do not know the last time they have eaten. You should not offer food again.
Protocol variation is usually about fasting time (again, for mice you should not go beyond 4-6h). Otherwise, they are subjected to hypoglycemia after insulin ip. The second variation is the insulin dose (from 0,5-1,0 IU/Kg), depending on mice strain.
See if the attachments can help you.
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According to common soil hypothesis metabolic diseases are associated with each other due to underlying insulin resistance.
What is your take on that?
Inherited metabolic disorders are genetic conditions that result in metabolism problems. If it's can considered as linking so most people with inherited metabolic disorders have a defective gene that results in an enzyme deficiency. There are hundreds of different genetic metabolic disorders, and their symptoms, treatments, and prognoses vary widely.
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Dear All,
I am looking for papers or evidences for loss of insulin receptor in case of diabetes. I am interetsed to know more about insulin resistance development based on insulin receptor loss. Please give your comments on the same.
Thanks and reagrds,
Diptiman
These might be helpful...
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Diabetes mellitus has two distinct but quite differet forms. Type 1 due to lack id insulin production and type 2 an excess of glucose that insulin production can no longer control. Insulin resistance is cited as an issue when the physiological issue is too much glucose. Until glucose consumption is targetted in the management of type 2 diabetes mellitus, the underlying cause will not be addressed, contributing to phararmacologic and surgical interventions when diet modifiction is what is needed
I guess IT CAN, but still diabetes remain the disease of lifestyle, so NOT ALWAYS
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I would like to induce diabetes in swiss mice by fructose in the drinking water, but it is hard to find literature about it. Protocols are scarce. Also, in the studies that have attempted the protocols vary too much regarding the lenght of time to induce diabetes and fructose concentration. Also, does anyone knows if there are differences in the time to achieve glucose/ insulin resistance among male and female mice?
Get a look on this paper please. May be it will help:
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Hi,
I had met with the statement that Alzheimer's disease is type 3 diabetes and that the insulin resistance damages brain cells. While in the literature the brain is described as an insulin independent organ.
What is your opinion?
Do you know some papers that can dispell doubts?
Mikołaj
Dear Mikolaj,
This is a great question. We are well known that most of our body cells have glucose transporter system which mostly mediated by insulin. However, a number of cells uptakes glucose without insulin mediation. Thus, in hyperglycaemic conditions such as insulin resistance these cells are more affected and most of diabetes complications observe in these cells due to glucose over uptake ...thus, midlife type 2 diabetes was not simply a vascular risk factor but rather had a more general negative effect on brain integrity. It could directly affect nerve cell and synapse physiology, perhaps by enhancing Alzheimer-type neurodegeneration, or the loss of brain volume could be separate though additive with Alzheimer pathology.
All the best,
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Does anyone have papers relating fasting insulin levels and associated CVD risks?
Dear Terun,
Maybe the following reviews will help you on the subject:
Xun P, Wu Y, He Q, He K. Fasting insulin concentrations and incidence of hypertension, stroke, and coronary heart disease: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2013;98(6):1543-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831539/pdf/ajcn9861543.pdf
Zhang X, Li J, Zheng S, Luo Q, Zhou C, Wang C. Fasting insulin, insulin resistance, and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis. Biosci Rep 2017;37(5):BSR20170947. http://www.bioscirep.org/content/37/5/BSR20170947.full-text.pdf
Best regards from Germany,
Martin
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Hi all,
I would like to calculate the hepatic insulin resistance index proposed by Abdul-Ghani et al., (2007) using the following formula with values from an OGTT:
HIRI = (glucose0–30[AUC] x insulin0–30[AUC]).
I have calculated the AUC between baseline and 30 minutes using the trapezoid rule, with glucose expressed in mmol/L and insulin expressed in pmol/L. Is this correct? or do I need to use other units of measurements?
I am asking this questions as I have seen this formula used in numerous research articles but there is great discrepancy between the results in each.
Thank you in advance.
Thank you all very much for your recommendations and research papers to read and reference. I really appreciate it!
Best regards,
Kiera
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Insulin resistance condition in which the receptor is mutated is it just a feedback mechanism of less use of ATP??
Dear Pranab
Good day. As for as mechanism of insulin resistance in type-2 diabetes mellitus is concerned, I think the basic evidence emerged when researchers observed that hyperglycemia was associated with higher than normal insulin, which implied that the hyperinsulinemia was unable to dispose of the glucose. This led to the concept of “insulin resistance”.
Now your question needs underlying mechanism in subjects with insulin resistance. Coming to this, first its not just ATP to blame, the defects seem to have molecular basis leading to changes in both insulin receptor and further downstream effect.
The normal physiological insulin-insulin receptor pathway is depicted as: (ATTACHED AS FIGURE-1)
So pathology can result from beta cell dysfunction, insulin release kinetics, insulin, insulin receptor and further downstream actors.
1- Vollenweider P et al have demonstrated defects in downstream pathways affecting insulin receptor substrate (IRS) related phosphatidylinositol 3 (PIP3) activation, which further inhibits the PKC protein due to decrese tyrosine kinase phosphorylation.
Reference: Vollenweider P et al. Insulin resistance, defective insulin receptor substrate 2-associated phosphatidylinositol-3' kinase activation, and impaired atypical protein kinase C (zeta/lambda) activation in myotubes from obese patients with impaired glucose tolerance. Diabetes. 2002 Apr;51(4):1052-9.
2- Another pathway highlighted along with Vollenweider et al is that of p42(MAPK) & p44(MAPK) tyrosine phosphorylationwhich can lead to decrease glucose related uptake of glucose.
Reference: del Aguila LF et al. TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am J Physiol.1999 May;276(5 Pt 1):E849-55.
3- Mutations in insulin receptor are also common in diabetes.
Reference: Kusari J et al. Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles. J Biol Chem. 1991 Mar 15;266(8):5260-7.
4- Apart from glucose insulin resistance is also implicated in disturbing lipid metabolites leading to their ectopic deposition and poor folding of several protein and effects on immune response with increase release of inflammatory cytokines.
Reference: Samuel VT et al. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012 Mar 2;148(5):852-71. doi: 10.1016/j.cell.2012.02.017.
Finally pubmed data search as ome of which I have highlighted will provide you with enormous specific defects in insulin release in type-2 diabetes. Moreover, the evolving field of molecular pathology is discovering newer and newer mutations which actually play the producer and director’s role behind these apparent mechanisms. Much more to decipher in terms of molecular parthenogenesis.
Regards
Dr Sikandar
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Insulin resistance is considered as an important contributor, if not he sole cause of PCOS. But i believe there must be other tangible factors which cause insulin resistance. There are features of ladies and young girls which have all features of PCOS but no insulin resistance. Yes congenital adrenal hyperplasia can be one but still there are patients with PCOS like symptoms but no insulin resistance.
So what else can cause such features?
Thanks a lot José Fernando Díaz-Villanueva
But are there other contributors to PCOS other than insulin resistance because the points you mentioned are related to insulin resistance.
I have seen very typical PCOS phenotypes but with no insulin resistance or whatsoever, so can there be other factors leading to this PCOS phenotype?
Some genetically modified tendencies?
Some other diseases causing PCOS like patterns??
Regards
Dr Sikandar
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Insuli-Resistance and 2NBDG glucose uptake
Hi Andrew
i detailled below the protocol i used to induce insulino-resistance and assay 2-NBDG cell incorporation. Unfortunally, the values that i obtained was the same. is there any modifications i should do?
2-NBDG glucose uptake assay on insulin-resistant HepG2 cells
- Culture cells (2 x 104/well) in a black clear bottom 96-well microtiter plate in a final volume of 100 µL/well in presence of additional factors for viability/proliferation testing.
- Incubate cells overnight or 80-90% of confluence. The appropriate incubation time will depend on the individual cell type and cell concentrations used.Therefore, it is recommended to determine the optimal incubation time for a particular experiment.
- Carefully remove (decant) the overnight culture medium from adherent cells and add in each wells 100µL of fresh medium (without growth factors: FBS) containing 1 µM insulin in serum-free MEM (5.5 mM Glucose)
- Incubate the plate at 37°C for 24 hours in a humidified, 5% CO2 atmosphere
- Carefully remove (decant) the overnight culture medium from adherent cells and add in each wells 100µL of fresh medium low glucose (without growth factors: FBS) containing for each well the amount of sample (concentration) need for the experiment
- Incubate the plate at 37°C for 24h in a humidified 5% CO2 atmosphere
- Carefully remove (decant) the culture medium containing samples from adherent cells and add in each wells 100µL of fresh medium low glucose (without growth factors: FBS) containing 0.1 µM insulin in serum-free MEM (5.5 mM glucose)
- Incubate the plate at 37°C for 30 minutes in a humidified 5% CO2 atmosphere
- Then, add in each wells 100 µL of 2-NBDG (40 µM) prepared on PBS (1% BSA)
- Incubate the plate at 37°C for 30 minutes in a humidified 5% CO2 atmosphere
- Washed cells two times with 200 µL of ice-cold PBS to stop uptake
- Add in each wells 100 µL of PBS
- Measure the 2-NBDG fluorescence intensity on a fluorescence microplate reader at 465 nm excitation and 540 nm emission wavelengths.
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Does the increased levels of Insulin is always associated with Insulin resistance?
Sikandar, yes, most MD doctors are testing hemoglobin A1C which is glycated red blood cells. Since RBC live for 3 months the hgA1c gives, a pretty good average of fasting glucose for the last 3 months. Glycated proteins produce AGE Advanced Glycated End products that accelerate aging. And then there is glycated insulin, that will be the most important test in the future - see:
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What are the best studies in this field?
Maybe the following papers will help you:
1. Shi-Xiong Tan, Kelsey H. Fisher-Wellman, Daniel J. Fazakerley, Yvonne Ng, Himani Pant, Jia Li, Christopher C. Meoli, Adelle C. F. Coster, Jacqueline Stöckli§4, and David E. James. Selective Insulin Resistance in Adipocytes. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 290, NO. 18, pp. 11337–11348, May 1, 2015
2. Zechner R, Zimmermann R, Eichmann TO, et al. FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling. Cell Metabolism. 2012;15(3):279-291. doi:10.1016/j.cmet.2011.12.018.
3. Philip G. McTernan, Alison L. Harte, Leah A. Anderson , Allan Green, Stephen A. Smith, Julie C. Holder, Anthony H. Barnett, Margaret C. Eggo, Sudhesh Kumar. Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro.Diabetes May 2002, 51 (5) 1493-1498 .
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i have read several articles and there were contradictions. The main problem was about adipose tissue and obesity. As adipocyte grows, it would secrete MCP-1 or other adipokine that attract macrophages. Consequently attracted macrophages would secrete various inflammation cytokines such as TNF-alpha. Those cytokines would decrease insulin sensitivity in adipose tissue and muscle. On top of that it would also decrease ppar gamma gene expression and increase lipolysis. As a result concentration of free fatty acid increases. However, the obese are getting more fat and have a larger adipose tissue than lean subject or mouse. Can anyone solve this contradiction
regards
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I have to measure the lactate concentration in mouse blood over time. There seems to be several lactameters on the market (more or less similar to glycometers), however, the manufactures are not typical lab providers. Thus, it is difficult to know which to go for/trust.
I’m curious, what method did you end up using? I’m currently using the iSTAT device to measure different blood gases along with lactate, but I‘m seeing odd lactate levels, even in my control mice. Taking blood from a cardiac puncture during harvest and immediately analyzing. Wondering if there is a more accurate way to measure for mice as this device is typically used for human patients.
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As diabetes (type 1 diabetes and type 2 diabetes) is metabolic disease and very complex, it involved in dysregulation of carbohydrates, proteins and fats metabolisms. So, there is macro- & microvascular complications in the body like cardiovacular problems, coronary artery diseases, retinopathy, nephropthy and peripheral neuropthy, some others etc, furthermore, its mechanism involved hyperglycemia, insulin resistance and some other factors responsible for these complications. Please provide review articles and publications latest to cover all these situations.
If it may help...
Popović-Djordjević J.B., Jevtić I.I., Stanojković, T. P. (2018) Antidiabetics: Structural Diversity of Molecules with a Common Aim, Current Medicinal Chemistry.
DOI : 10.2174/0929867325666171205145309
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Beyond checking Glycated hemoglobin (Hb A1C) I want to start checking both glycated albumin and insulin. Glycated albumin will indicate the risk of rising amounts of ionized calcium; glycated insulin will establish the risk of insulin resistance that develops into type II Diabetes
Dear Carlos
Epinex is developping a test for glycated albumin. Not yet FDA approved.
provide devices for POC measurement of Hb A1c that I am aware of. I am sure there are more on the market. Kind regards, Michaela
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Whether diabetes management is a problem but there is lack of diagnosis of complications, how should it be emphasized on the early basis and manage with special criteria. i think many factors are there if we restricted hyperglycemic control and insulin resistance, there are unknown factors that can cause these problems with restricted control too, so if early diagnosis is made then there is chance to further inhibit the complications of diabetes.
Dear Abdul,
Maybe the following papers will help you:
Moore DJ, Gregory JM, Kumah-Crystal YA, Simmons JH. Mitigating micro-and macro-vascular complications of diabetes beginning in adolescence. Vasc Health Risk Manag 2009;5:1015-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788594/pdf/vhrm-5-1015.pdf
Zimmerman RS. Diabetes Mellitus: Management of Microvascular and Macrovascular Complications. Cleveland Clinic - Center for Continuing Education. 2016. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/diabetes-mellitus/
Donaghue KC, Wadwa RP, Dimeglio LA, Wong TY, Chiarelli F, Marcovecchio ML, Salem M, Raza J, Hofman PL, Craig ME; International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice Consensus Guidelines 2014. Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2014;15 Suppl 20:257-269. http://www.asped.org/chapters/18-Microvascular%20and%20macrovascular%20complications%20in%20children%20and%20adolescents.pdf
All the best,
Martin
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Is it possible for insulin sensitivity to change within 5 hours of consuming an antioxidant nutritional intervention?
I completly agree that insulin sensitivity is very dinamically altered by many physiologically or pathologic conditions. In dogs, secondary diabetes as result of higuer progesterone and GH levels is very commom during diestrus in intact females. When we remove the source of those antagonic hormonal stimuli, many bitches achiev diabetes remission, sometimes few days after surgery. This paper may help...
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I have given a bolus (drink containing sugar) and measured HOMA and QUICKI indexes post-bolus for up to 5hrs every hour.
I know both HOMA and QUICKI work on fasting insulin and glucose values, does this mean my data is invalid as I have given my participants a drink to consume?
No, HOMA and QUICKI basically reflect hepatic insulin resistance while the measures after a glucose challenge rather reflect whole body insulin resistance (muscle, fat etc) or beta cell function. There are other indices for insulin/glucose dynamics such as insulinogenic index, matsuda etc
see
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I am currently studying the db/db K strain and have a project with updates regarding my transmission electron microscopic findings
and I have found that in this obese insulin resistant model with persistent elevations of glucose making it a definite type 2 DM model that has preexisting obesity and insulin resistance that the astrocyte
become separated from the NVU Endothelial basement membrane and become retracted as well. These TEM finding obliterate the normal astrocyte corona as found in control models regarding studies of the NVU (neurovascular unit). Do you think these findings are compatible with impaired signaling of the other NVU in the midbrain cortex as in my project findings.
Sincerely,
M. R. (Pete) Hayden, MD
mrh29pete@gmail.com - if you would prefer to answer by e-mail correspondence.
Dr. Hyden, this is a very recent multidisciplinary project, we are working on the identification of the components of the sample through chromatography, spectrometry and magnetic resonance. We are starting studies in the hyperglycemic mouse with a skin lesion that includes the destruction of the epidermis and deep dermis. We intend to evaluate the regenerative activity of the skin layers, vascularization, etc., in these animals treated with the substance. We do not have publications so far and we are looking for financing to continue advancing in the coming years. So we keep in communication by RG or email (rogarcia@uacam.mx)
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Some researchers claim that it happens, some other not.
The link is an association not causal. Do patients who are more likely to use sweeteners have the profile of people who would tend to have higher rates of insulin resistance?- confounder, not causal.
Even if it is causal, then the signal is not very strong.
Just an opinion.
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