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Study of islet morphology. After 12 weeks on CD or HFD, the pancreas was extracted, and 4 mm pancreas sections were stained with DAPI (4’,6-Diamidino-2-Phenylindole (double stranded DNA staining) and insulin-specific antibodies to identify the islets. In (a) the islet size, (b) the islet circularity, (c) the number of beta cells per islet, (d) the beta cell density in the islet and (e) the total beta cell area (%) per total islet area are shown. The results are representative of at least three sections per animal, with a total of at least three animals for each WT and KO group. p values were calculated by two-way ANOVA with a Bonferroni post-test (* p < 0.05, ** p < 0.01). Data are presented as individual data points with their respective means.
Source publication
Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-o...
Citations
... The relationship between CAV-1 and high-fat diets has been shown in knockout mice. The available investigations showed that mice with polymorphisms in this gene had resistance to weight gain, hyperinsulinemia, and accumulation of epididymal fat following a high-fat diet [36][37][38]. These findings indicate that caveolin gene polymorphisms are closely related to diets and metabolic factors in an obesity-promoting environment. ...
Background and objective
Studies have shown that Caveolin gene polymorphisms (CAV-1) are involved in chronic diseases, such as metabolic syndrome. Moreover, the dietary insulin index (DII) and dietary insulin load (DIL) have been shown to potentially elicit favorable effects on cardiovascular disease (CVD) risk. Therefore, this study sought to investigate the effect of DII DIL and CAV-1 interaction on CVD risk factors.
Methods
This cross-sectional study consisted of 333 overweight and obese women aged 18–48 years. Dietary intakes, DII, and DIL were evaluated using the 147-item food frequency questionnaire (FFQ). Serum profiles were measured by standard protocols. The CAV-1 rs 3,807,992 and anthropometric data were measured by the PCR–RFLP method and bioelectrical impedance analysis (BIA), respectively. Participants were also divided into three groups based on DII, DIL score, and rs3807992 genotype.
Results
This comparative cross-sectional study was conducted on 333 women classified as overweight or obese. Participants with A allele for the caveolin genotype and higher DII score showed significant interactions with high-density lipoprotein (HDL) (P for AA = 0.006 and P for AG = 0.019) and CRI-I (P for AA < 0.001 and P for AG = 0.024). In participants with AA genotype and greater DII score, interactions were observed in weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, CRI-II, fat-free mass (FFM), and skeletal muscle mass (SMM) (P < 0.079). Those with higher DIL scores and AA genotype had higher weight (P = 0.033), FFM (P = 0.022), and SMM (P = 0.024). In addition, DIL interactions for waist/hip ratio (WHR), waist circumference (WC), triglyceride (TG), CRI-I, and body fat mass (BFM) among individuals with AA genotype, while an HDL interaction was observed in individuals with AG and AA (P < 0.066).
Conclusion
The findings of the present study indicate that people who carry the caveolin rs3807992 (A) allele and have greater DII and DIL scores are at higher risk for several cardiovascular disease and metabolic syndrome biomarkers. These results highlight that diet, gene variants, and their interaction, should be considered in the risk evaluation of developing CVD.
... For example, CAV1 gene, which encodes for caveolin 1, the main protein component of the caveolae plasma membranes found in most cells including beta cells, was also found to be up-regulated in islets from 7-day-old pigs compared to islets from 3-day-old pigs. Calveolin 1 was reported to participate in the regulation of insulin secretion, and recently, it was also shown to regulate insulin receptor internalization and ERK activation in human and mouse beta cells, implicating calveolin 1 is an important player in beta cell physiology (33)(34)(35). ANXA1 gene, which codes for annexin A1 protein, a membrane-localized protein that binds phospholipids and has anti-inflammatory activity has been shown to be a key modulator of mesenchymal stromal cell-mediated improvements in islet function (36). Treatment of mouse islets with annexin A1 resulted in an increase in high glucose-stimulated insulin secretion. ...
The yield, cell composition, and function of islets isolated from various ages of neonatal pigs were characterized using in vitro and in vivo experimental models. Islets from 7- and 10-day-old pigs showed significantly better function both in vitro and in vivo compared to islets from 3- and 5-day-old pigs however, the islet yield from 10-day-old pigs were significantly less than those obtained from the other pigs. Since islets from 3-day-old pigs were used in our previous studies and islets from 7-day-old pigs reversed diabetes more efficiently than islets from other groups, we further evaluated the function of these islets post-transplantation. B6 rag-/- mouse recipients of various numbers of islets from 7-day-old pigs achieved normoglycemia faster and showed significantly improved response to glucose challenge compared to the recipients of the same numbers of islets from 3-day-old pigs. These results are in line with the findings that islets from 7-day-old pigs showed reduced voltage-dependent K⁺ (Kv) channel activity and their ability to recover from post-hypoxia/reoxygenation stress. Despite more resident immune cells and immunogenic characteristics detected in islets from 7-day-old pigs compared to islets from 3-day-old pigs, the combination of anti-LFA-1 and anti-CD154 monoclonal antibodies are equally effective at preventing the rejection of islets from both age groups of pigs. Collectively, these results suggest that islets from various ages of neonatal pigs vary in yield, cellular composition, and function. Such parameters may be considered when defining the optimal pancreas donor for islet xenotransplantation studies.
... In another word, T2DM will never develop until pancreatic β-cells fail to cover insulin needs of tissues. A previous study has shown that impairment of serum Cav-1 is associated with a significant decrease in β-cell death in mice (22). In addition, silencing Cav-1 gene promotes the proliferation of pancreatic βcell, decreases apoptosis, and encourages insulin secretion (23). ...
... The current study has provided strong evidence that the significant prolonged decrease of serum Cav-1 concentrations in patients with T2DM is associated with a poor glycaemic control. Although, serum Cav-1 was the focus of many previous studies (14,16,18,21,22,23,24), however, this is the first study targeted Arabs, and the first to link low serum Cav-1 concentrations with the poorer prognosis in patients with T2DM. In addition, the results of the current study suggest that Cav-1 has the potential to be a therapeutic target in patients with T2DM and can be used as effective prognostic marker in the management of T2DM. ...
... Although the exact mechanism linking TGF-β with β-cell dysfunction is not yet known, however it was suggested that Cav-1 and TGFβ working in two different directions. Thus, knocking down Cav-1 gene and /or inhibit its expression resulting in a significant decrease in β-cell death (22), promotes pancreatic β-cells proliferation and increases insulin secretion under normal physiological glucose levels (23) and may trigger the up-regulation of metabolic diseases related genes (25). Insulin resistance and a defective of insulin receptor were observed in adipose tissue obtained from Cav-1 deficient mice (28). ...
... In another word, T2DM will never develop until pancreatic β-cells fail to cover insulin needs of tissues. A previous study has shown that impairment of serum Cav-1 is associated with a significant decrease in β-cell death in mice (22). In addition, silencing Cav-1 gene promotes the proliferation of pancreatic βcell, decreases apoptosis, and encourages insulin secretion (23). ...
... The current study has provided strong evidence that the significant prolonged decrease of serum Cav-1 concentrations in patients with T2DM is associated with a poor glycaemic control. Although, serum Cav-1 was the focus of many previous studies (14,16,18,21,22,23,24), however, this is the first study targeted Arabs, and the first to link low serum Cav-1 concentrations with the poorer prognosis in patients with T2DM. In addition, the results of the current study suggest that Cav-1 has the potential to be a therapeutic target in patients with T2DM and can be used as effective prognostic marker in the management of T2DM. ...
... Although the exact mechanism linking TGF-β with β-cell dysfunction is not yet known, however it was suggested that Cav-1 and TGFβ working in two different directions. Thus, knocking down Cav-1 gene and /or inhibit its expression resulting in a significant decrease in β-cell death (22), promotes pancreatic β-cells proliferation and increases insulin secretion under normal physiological glucose levels (23) and may trigger the up-regulation of metabolic diseases related genes (25). Insulin resistance and a defective of insulin receptor were observed in adipose tissue obtained from Cav-1 deficient mice (28). ...
Background:
The fluctuation in serum caveolin-1 (Cav-1) concentrations is an important indicator of many diseases. Irrespective of the actual cause, a significant reduction of serum Cav-1 is associated with a significant increase in insulin secretion and hyperinsulinemia. The aim of the current study was to evaluate the relationship between serum Cav-1, serum vaspin and visfatin in newly diagnosed men with T2DM.
Methods:
Eighty-two newly diagnosed men with T2DM were matched for age and body mass indexes (BMIs) with a similar number of non-diabetic men. Serum Cav-1, vaspin and visfatin were assessed through enzyme-linked immunosorbent assay. Fasting serum glucose (FSG), glycohaemoglobin A1C (HbA1c) were both measured using automated method. In addition, waist-circumferences, waist-hip ratio, systolic (SBP), and diastolic blood pressure (DBP) were also obtained.
Results:
Serum concentration of Cav-1(ng/mL) was significantly low in men newly diagnosed with T2DM, (2.334±0.7627) compared with non-diabetic controls (4.321±1.143), p< 0.0001. In contrast, patients with T2DM exhibited significantly higher serum concentrations of vaspin and visfatin (ng/mL), 142.4±60.53) and 2.99±1.091), than controls, 81.53±39.32) and 1.456±0.654), respectively, p< 0.0001. Expectedly, patients with T2DM have significantly higher FSG, HbA1c, systolic blood pressure (SBP), and diastolic blood pressure (DBP).
Conclusion:
There was an inverse significant relationship between Cav-1 and vaspin, visfatin, HbA1c, FSG, and hypertension. This study suggests that serum Cav-1 can be used as a diagnostic marker to predict T2DM in individuals and families under high risk.
... in different cohorts such as Caucasian and Hispanic [40], and other genetic variants have been associated with insulin resistance [41], too. Other findings suggested that CAV1 is related with the response of beta cell to different hypocaloric diets in animal models [42]. Fourthly, some studies showed that the gene encoding solute carrier family 12 member 3 (SLC12A3) is a typical candidate related with arterial hypertension in obese subjects, and its under expression could prevent this comorbidity in obese subjects [43]. ...
Background:
Few studies have examined gene expression in peripheral blood mononuclear cells (PBMCs) after a dietary intervention.
Objective:
Our study is aimed at evaluating in a pilot study the peripheral blood gene expression in obese patients after weight loss secondary to a hypocaloric Mediterranean diet.
Design:
A sample of 11 obese subjects without metabolic syndrome was enrolled. Biochemical, anthropometric parameters and microarray analysis were performed at baseline and after 6 months of dietary intervention.
Results:
The mean age was 43.1 ± 6.3 years, and the mean body mass index (BMI) was 38.6 ± 8.1 kg/m2. All the next improvements were statistically significant: body weight -7.4 ± 1.9 kg, BMI -2.5 ± 0.2 kg, fat mass -5.7 ± 1.2 kg, waist circumference -5.8 ± 1.2 cm, triglycerides -17.4 ± 6.5 mg/dl, C-reactive protein -3.1 ± 1.5 mg/dL, insulin -2.1 ± 1.0 mUI/L, and HOMA-IR -0.7 ± 0.2 units. We identified 634 differentially expressed genes: 262 genes with relative higher expression levels and 372 with lower expression levels. Cluster analysis showed 35 genes in nutritional disease and 17 genes in endocrine system. The most relevant gene was thyroid peroxidase (TPO), and this gene was overexpressed, and the next genes carbonic anhydrase VI (CA6), caveolin protein 1 (CAV1) and solute carrier family type 12 (SLLC12A3), soluble carrier family type 12 (SLLC12A3), beta 3 receptor (ADRB3), and glutamate receptor ionotropic N methyl D aspartate 2 A (GRIN2A) were all underexpressed.
Conclusion:
In PBMC from obese patients after a diet with a Mediterranean pattern, the expression of 634 genes, of the endocrine system and of nutritional disease, is modified.
... Accordingly, our five screened-out ferroptosis-related genes showed high reliability. CAV1 is a membrane-bound scaffold protein family which is related to CAV2 and CAV3 protein families (Lillo Urzúa et al., 2020). CAV1 is widely expressed in lung tissues including alveolar epithelial cells, endothelial cells, fibroblasts, and smooth muscle cells. ...
Objective: Ferroptosis has an important role in developing pulmonary fibrosis. The present project aimed to identify and validate the potential ferroptosis-related genes in pulmonary fibrosis by bioinformatics analyses and experiments.
Methods: First, the pulmonary fibrosis tissue sequencing data were obtained from Gene Expression Omnibus (GEO) and FerrDb databases. Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between the normal control group and the pulmonary fibrosis group and extract ferroptosis-related DEGs. Hub genes were screened by enrichment analysis, protein-protein interaction (PPI) analysis, and random forest algorithm. Finally, mouse pulmonary fibrosis model was made for performing an exercise intervention and the hub genes’ expression was verified through qRT-PCR.
Results: 13 up-regulated genes and 7 down-regulated genes were identified as ferroptosis-related DEGs by comparing 103 lung tissues with idiopathic pulmonary fibrosis (IPF) and 103 normal lung tissues. PPI results indicated the interactions among these ferroptosis-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment and Genome-Ontology (GO) enrichment analyses showed that these ferroptosis-related genes involved in the organic anion transport, response to hypoxia, response to decrease oxygen level, HIF-1 signaling pathway, renal cell carcinoma, and arachidonic acid metabolism signaling pathway. The confirmed genes using PPI analysis and random forest algorithm included CAV1, NOS2, GDF15, HNF4A, and CDKN2A. qRT-PCR of the fibrotic lung tissues from the mouse model showed that the mRNA levels of NOS2 and GDF15 were up-regulated, while CAV1 and CDKN2A were down-regulated. Also, treadmill training led to an increased expression of CAV1 and CDKN2A and a decrease in the expression of NOS2 and GDF15.
Conclusion: Using bioinformatics analysis, 20 potential genes were identified to be associated with ferroptosis in pulmonary fibrosis. CAV1, NOS2, GDF15, and CDKN2A were demonstrated to be influencing the development of pulmonary fibrosis by regulating ferroptosis. These findings suggested that, as an aerobic exercise treatment, treadmill training reduced ferroptosis in the pulmonary fibrosis tissues, and thus, reduces inflammation in the lungs. Aerobic exercise training initiate concomitantly with induction of pulmonary fibrosis reduces ferroptosis in lung. These results may develop our knowledge about pulmonary fibrosis and may contribute to its treatment.
... Showed that the A allele carriers were more odds of metabolic syndrome and its components (including abdominal obesity or high blood pressure) in individuals, and also, there was significant interaction between CAV 1 rs3807992 and SFA or PUFA on metabolic syndrome and its components [69]. The results of the Chung et al. study showed that the mean body in group fed a normal diet was lower than in group fed a high-fat diet, albeit in rats [70]. The study Mora-García et al. showed shown there was significant association between rs 926,198 and WHR but there was no association between rs 926198 and WC and WHtR [31]. ...
Background
It has been reported that dietary fats and genetic factors in individuals are associated with the pattern of fat distribution. This study aimed to evaluate the interaction between dietary fats intake and Caveolin1 (CAV-1) rs 3807s992 polymorphism with fat distribution in overweight and obese women.
Methods
A total of 221 participants were included in the current cross-sectional study. Body composition, biochemical parameters were evaluated by body composition analyzer and Pars Azmoon kits and genotypes determination was performed by PCR–RFLP, dietary fats were measured using a validated semi-quantitative food frequency questionnaire (FAQ).
Results
The frequency of GG, AA and AG genotypes were 53.1, 24.6, and 22.3%, respectively, and the mean intake of total dietary fat intake was 97.47 ± 36.87 g. There was positive significant interaction between total fat intake and AA genotype on visceral fat level ( p = 0.001), trunk fat ( p = 0.01) and waist circumference ( p = 0.05), positive significant interaction between total fat intake and AG genotype on the waist to hip ratio (WHR) ( p = 0.02) and visceral fat level ( p = 0.05), positive borderline significant interaction between saturated fatty acid and AA genotype on the trunk fat ( p = 0.06), and between trans-fatty acids and AG genotype on WHR ( p = 0.04), visceral fat level ( p = 0.01), and between monounsaturated fatty acid and AG genotype on WHR ( p = 0.04), and a borderline interaction between polyunsaturated fatty acid and AA genotypes on visceral fat level ( p = 0.06), negative significant interaction between AG genotypes and linolenic acid on WHR ( p = 0.04), borderline significant interaction between ALA and AG genotype on WHR ( p = 0.06).
Conclusions
Our findings showed that CAV-1 rs 3807992 polymorphism and dietary fats were associated with fat distributions in individuals.
... C-peptide, one of the lysis products of proinsulin, is secreted into the circulation in equal amounts to insulin [17]. Compared with insulin, C-peptide is more stable because it is less easily destroyed by the liver [18] and has a longer half-life [19]. Therefore, measuring C-peptide levels can better reflect the function of islet β cell synthesis and the secretion of endogenous insulin, which is widely used in clinical practice. ...
Background
Fasting C-peptide (FCP) has been shown to play an important role in the pathophysiology of mood disorders including depression and schizophrenia, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between FCP and PSD at 6 months after acute ischemic-stroke onset among Chinese subjects.
Methods
A total of 656 stroke patients were consecutively recruited from three hospitals of Wuhan city, Hubei province. Clinical and laboratory data were collected on admission. PSD status was evaluated by DSM-V criteria and 17-item Hamilton Rating Scale for Depression (HAMD-17) at 6 months after acute ischemic stroke. The χ2-test, Mann-Whitney U-test, and t-test were used to check for statistical significance. Multivariate logistic regression model was used to explore independent predictor of PSD.
Results
In the univariate analysis, significant differences were found between the PSD and non-PSD groups in terms of FCP level ( p = 0.009). After multivariate adjustments, FCP remained a significant independent predictor of PSD, with an adjusted odds ratio of 1.179 (95%CI: 1.040–1.337, p = 0.010).
Conclusions
Higher FCP levels on admission were found to be associated with PSD at 6 months after acute ischemic-stroke onset. For stroke patients, doctors should pay attention to the baseline FCP for screening high-risk PSD in clinical practice.
Lipotoxicity-induced pancreatic β cell damage is a strong predictor of type 2 diabetes mellitus (T2DM). Our previous work showed that Caveolin-1 (Cav-1) depletion decreased β-cell apoptosis and improved β-cell viability. Further microarray analysis indicated significant changes in the expression of genes related to fatty acid metabolism and inflammation. The objective of this study was to explore the role of Cav-1 in intracellular lipid accumulation and inflammation in β cells under lipotoxic conditions. Here, we established a β-cell-specific Cav-1 knockout (β-Cav-1 KO) mouse model and a CAV-1 depleted β cell line (NIT-1). We found that Cav-1 silencing significantly reduced palmitate (PA)-induced intracellular triglyceride (TG) accumulation and decreased proinflammatory factor expression in both the mouse and cell models. Further mechanistic investigation revealed that amelioration of lipid metabolism was achieved through the downregulation of lipogenic markers (SREBP-1c, FAS and ACC) and upregulation of a fatty acid oxidation marker (CPT-1). Meanwhile, decrease of inflammatory cytokines (IL-6, TNF-α, and IL-1β) secretion was found with the involvement of the IKKβ/NF-κB signaling pathways. Our findings suggest that Cav-1 is of considerable importance in regulating lipotoxicity-induced β-cell intracellular lipid accumulation and inflammation.
Methionine restriction (MR) improves glucose metabolism. In skeletal muscle, H19 is a key regulator of insulin sensitivity and glucose metabolism. Therefore, this study aims to reveal the underlying mechanism of H19 upon MR on glucose metabolism in skeletal muscle. Middle-aged mice were fed MR diet for 25 weeks. Mouse islets β cell line β-TC6 cells and mouse myoblast cell line C2C12 cells were used to establish the apoptosis or insulin resistance model. Our findings showed that MR increased B-cell lymphoma-2 (Bcl-2) expression, deceased Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate-specific proteinase-3 (Caspase-3) expression in pancreas, and promoted insulin secretion of β-TC6 cells. Meanwhile, MR increased H19 expression, insulin Receptor Substrate-1/insulin Receptor Substrate-2 (IRS-1/IRS-2) value, protein Kinase B (Akt) phosphorylation, glycogen synthase kinase-3β (GSK3β) phosphorylation, and hexokinase 2 (HK2) expression in gastrocnemius muscle and promoted glucose uptake in C2C12 cells. But these results were reversed after H19 knockdown in C2C12 cells. In conclusion, MR alleviates pancreatic apoptosis and promotes insulin secretion. And MR enhances gastrocnemius muscle insulin-dependent glucose uptake and utilization via the H19/IRS-1/Akt pathway, thereby ameliorating blood glucose disorders and insulin resistance in high-fat-diet (HFD) middle-aged mice.
