Ranganath Muniyappa

The National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States

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Publications (39)188.33 Total impact

  • Ranganath Muniyappa, Pothur R Srinivas
    Diabetes 11/2014; 63(11):3587-9. · 7.90 Impact Factor
  • Ranganath Muniyappa, James R Sowers
    Diabetes 04/2014; 63(4):1194-7. · 7.90 Impact Factor
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    ABSTRACT: OBJECTIVE Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy.RESEARCH DESIGN AND METHODS In a prospective, open-label, currently ongoing study we studied the effects of leptin replacement on β-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. β-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT.RESULTSThere was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, β-cell glucose sensitivity, rate sensitivity, or insulin clearance.CONCLUSIONS In contrast to the suppressive effects of leptin on β-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.
    Diabetes care 02/2014; · 7.74 Impact Factor
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    ABSTRACT: Context:Disruption of the Gsαmaternal allele leads to severe obesity and insulin resistance in mice and early-onset obesity in patients with pseudohypoparathyroidism (PHP) type 1a. However, insulin resistance and glucose metabolism have not been systematically characterized in patients with PHP1a.Objective, Design, and Setting:In a cross-sectional, case-control study, we examined insulin sensitivity, β-cell function, energy expenditure, and sympathetic nervous system activity (SNA) in adults with PHP1a.Study Participants:PHP1a patients (n=8) and healthy control subjects (n=24) matched for age (41 ± 7 vs. 41 ± 7 yr [mean ± SD]), gender, and percent body fat.Methods:Insulin sensitivity (SI), acute insulin response to glucose, and disposition index (DI) were assessed during an FSIVGTT. Oral glucose insulin sensitivity (OGIS) was measured during a mixed meal. Energy expenditure was measured using whole room indirect calorimetry. Body composition was assessed via dual-energy x-ray absorptiometry and SNA by measuring 24-hr urinary catecholamine concentrations.Results:Results: PHP1a patients were less insulin-sensitive than their matched controls based upon SI and OGIS. Non-diabetic PHP1a patients tended to have a lower SI (p = 0.09) and reduced OGIS (p = 0.03). DI, a composite measure of β-cell function also tended to be lower in patients (p=0.07). Total caloric intake, resting energy expenditure (REE), total EE, meal-induced thermogenesis, and 24-hr urinary catecholamine concentrations were not significantly different between the groups.Conclusions:Adults with PHP-1a have reduced insulin sensitivity compared with their matched controls that may contribute to the pathogenesis of glucose intolerance and diabetes in these patients.
    The Journal of Clinical Endocrinology and Metabolism 09/2013; · 6.31 Impact Factor
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    ABSTRACT: OBJECTIVE We examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals.RESEARCH DESIGN AND METHODS In a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT).RESULTSSelf-reported cannabis use was: 9.5 (2-38) years; joints/day: 6 (3-30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups.CONCLUSIONS Chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance.
    Diabetes care 03/2013; · 7.74 Impact Factor
  • Ranganath Muniyappa, James R Sowers
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    ABSTRACT: Insulin resistance is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular diseases. Insulin exerts pro- and anti-atherogenic actions on the vasculature. The balance between nitric oxide (NO)-dependent vasodilator actions and endothelin-1- dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. During insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1 and lead to endothelial dysfunction. Insulin sensitizers that target pathway-selective impairment in insulin signaling are known to improve endothelial dysfunction. In this review, we discuss the cellular mechanisms in the endothelium underlying vascular actions of insulin, the role of insulin resistance in mediating endothelial dysfunction, and the effect of insulin sensitizers in restoring the balance in pro- and anti-atherogenic actions of insulin.
    Reviews in Endocrine and Metabolic Disorders 01/2013; · 4.58 Impact Factor
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    Ranganath Muniyappa, James R Sowers
    Diabetes 09/2012; 61(9):2225-7. · 7.90 Impact Factor
  • Ranganath Muniyappa, Sahzene Yavuz
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    ABSTRACT: Metabolic actions of insulin to promote glucose disposal are augmented by nitric oxide (NO)-dependent increases in microvascular blood flow to skeletal muscle. The balance between NO-dependent vasodilator actions and endothelin-1-dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. Angiotensin II acting on AT(2) receptor increases capillary blood flow to increase insulin-mediated glucose disposal. In contrast, AT(1) receptor activation leads to reduced NO bioavailability, impaired insulin signaling, vasoconstriction, and insulin resistance. Insulin-resistant states are characterized by dysregulated local renin-angiotensin-aldosterone system (RAAS). Under insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Similarly, excess AT(1) receptor activity in the microvasculature may selectively impair vasodilation while simultaneously potentiating the vasoconstrictor actions of insulin. Therapeutic interventions that target pathway-selective impairment in insulin signaling and the imbalance in AT(1) and AT(2) receptor signaling in microvascular endothelium may simultaneously ameliorate endothelial dysfunction and insulin resistance. In the present review, we discuss molecular mechanisms in the endothelium underlying microvascular and metabolic actions of insulin and Angiotensin II, the mechanistic basis for microvascular endothelial dysfunction and insulin resistance in RAAS dysregulated clinical states, and the rationale for therapeutic strategies that restore the balance in vasodilator and constrictor actions of insulin and Angiotensin II in the microvasculature.
    Molecular and Cellular Endocrinology 06/2012; · 4.04 Impact Factor
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    ABSTRACT: Epigallocatechin gallate (EGCG), the major polyphenol in green tea, acutely stimulates production of nitric oxide (NO) from vascular endothelium to reduce hypertension and improve endothelial dysfunction in spontaneously hypertensive rats. Herein, we explored additional mechanisms whereby EGCG may mediate beneficial cardiovascular actions. When compared with vehicle-treated controls, EGCG treatment (2.5 μM, 8 h) of human aortic endothelial cells (HAEC) caused a ~three-fold increase in heme oxygenase-1 (HO-1) mRNA and protein with comparable increases in HO-1 activity. This was unaffected by pretreatment of cells with wortmannin, LY294002, PD98059 or L-NAME (PI 3-kinase, MEK and NO synthase inhibitors, respectively). Pretreatment of HAEC with SB203580 (p38 MAPK inhibitor) or siRNA knockdown of p38 MAPK completely blocked EGCG-stimulated induction of HO-1. EGCG treatment also inhibited tumor-necrosis-factor-α-stimulated expression of vascular cell adhesion molecule (VCAM)-1 and decreased adhesion of monocytes to HAEC. siRNA knockdown of HO-1, p38 MAPK or Nrf-2 blocked these inhibitory actions of EGCG. In HAEC transiently transfected with a human HO-1 promoter luciferase reporter (or an isolated Nrf-2 responsive region), luciferase activity increased in response to EGCG. This was inhibitable by SB203580 pretreatment. EGCG-stimulated expression of HO-1 and Nrf-2 was blocked by siRNA knockdown of Nrf-2 or p38 MAPK. Finally, liver from mice chronically treated with EGCG had increased HO-1 and decreased VCAM-1 expression. Thus, in vascular endothelium, EGCG requires p38 MAPK to increase expression of Nrf-2 that drives expression of HO-1, resulting in increased HO-1 activity. Increased HO-1 expression may underlie anti-inflammatory actions of EGCG in vascular endothelium that may help mediate beneficial cardiovascular actions of green tea.
    The Journal of nutritional biochemistry 11/2011; 23(9):1134-45. · 4.29 Impact Factor
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    ABSTRACT: Insulin resistance is associated with endothelial dysfunction. Because African-American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 African-American women, 18 white women) age- and body mass index (BMI)-matched (age: 37 ± 11 yr; BMI: 30 ± 6 kg/m(2)) women. Endothelial function, defined by percent change in brachial artery flow-mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although African-American women were less insulin-sensitive [insulin sensitivity index (mean ± SD): 3.6 ± 1.5 vs. 5.2 ± 2.6, P = 0.02], both fasting triglyceride (TG: 56 ± 37 vs. 97 ± 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC(0-6hr): 279 ± 190 vs. 492 ± 255 mg·dl(-1)·min(-1)·10(-2), P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups (P > 0.1 for group × time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function.
    AJP Endocrinology and Metabolism 11/2011; 302(2):E218-25. · 4.51 Impact Factor
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    Ranganath Muniyappa
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    ABSTRACT: Glucosamine (2-amino-2-deoxy-D-glucose), an amino monosaccharide derivative of glucose, is a precursor of the glycosaminoglycans and proteoglycans that make up articular cartilage. The notion that augmenting the intake of the precursor molecule, glucosamine, may directly stimulate articular proteoglycan synthesis to modulate osteoarthritis has provided the rationale for its widespread use. Theoretically, exogenous glucosamine may augment glycosaminoglycan synthesis in cartilage. There is a simultaneous theoretical concern that it might also induce insulin resistance in insulin-sensitive tissues.In a previous issue of DMRR, Simon et al. conclude that typical doses of oral glucosamine have no significant effects on glucose metabolism or insulin sensitivity. On the basis of the results from clinical, animal, and cell-based studies they conclude that oral glucosamine neither augments the hexosamine biosynthetic pathway nor reduces insulin-mediated glucose uptake. In recent meta-analyses restricted to well-designed randomized controlled trials that include adequate allocation concealment or to non-industry-funded studies, oral glucosamine fails to show any significant clinical benefit in individuals with osteoarthritis. These data should raise serious questions from patients and their health care providers about its continued use. Published 2011 by John Wiley & Sons, Ltd.
    Diabetes/Metabolism Research and Reviews 03/2011; 27(3):233-4. · 2.97 Impact Factor
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    ABSTRACT: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. DESIGN, SETTING, AND INTERVENTIONS: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H(2)O(2). Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption.
    The Journal of Clinical Endocrinology and Metabolism 02/2011; 96(5):E782-92. · 6.31 Impact Factor
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    ABSTRACT: The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SI(Clamp) (r ≈ 0.4-0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies.
    Endocrinology 02/2011; 152(2):414-23. · 4.72 Impact Factor
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    ABSTRACT: In animal studies, testosterone decreases, whereas estrogen increases, cortisol production. In one clinical study, short-term testosterone replacement attenuated corticotrophin-releasing hormone-stimulated cortisol secretion during leuprolide-induced hypogonadism in young men. The effects of longer term testosterone treatment on spontaneous cortisol secretion in younger or older men are unknown. In a randomized, double-masked placebo-controlled study, we assessed the effects of testosterone supplementation (100 mg intramuscular every 2 week) for 26 weeks on nocturnal cortisol secretory dynamics in healthy older men. Testosterone administration increased early morning serum concentrations of free testosterone by 34%, decreased sex hormone-binding globulin by 20%, and did not alter early morning concentrations of cortisol-binding globulin or cortisol compared with placebo treatment. Testosterone did not significantly alter nocturnal mean and integrated cortisol concentrations, cortisol burst frequency, mass/burst, basal secretion, pulsatile cortisol production rate, pattern regularity, or approximate entropy. We conclude that low-dose testosterone supplementation for 26 weeks does not affect spontaneous nocturnal cortisol secretion in healthy older men.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2010; 65(11):1185-92. · 4.31 Impact Factor
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    ABSTRACT: Insulin resistance is highly prevalent in Asian Indians and contributes to worldwide public health problems, including diabetes and related disorders. Surrogate measurements of insulin sensitivity/resistance are used frequently to study Asian Indians, but these are not formally validated in this population. In this study, we compared the ability of simple surrogate indices to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In this cross-sectional study of Asian-Indian men (n = 70), we used a calibration model to assess the ability of simple surrogate indices for insulin sensitivity [quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment (HOMA2-IR), fasting insulin-to-glucose ratio (FIGR), and fasting insulin (FI)] to predict an insulin sensitivity index derived from the reference glucose clamp method (SI(Clamp)). Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction as well as leave-one-out cross-validation-type RMSE of prediction (CVPE). QUICKI, FIGR, and FI, but not HOMA2-IR, had modest linear correlations with SI(Clamp) (QUICKI: r = 0.36; FIGR: r = -0.36; FI: r = -0.27; P < 0.05). No significant differences were noted among CVPE or RMSE from any of the surrogate indices when compared with QUICKI. Surrogate measurements of insulin sensitivity/resistance such as QUICKI, FIGR, and FI are easily obtainable in large clinical studies, but these may only be useful as secondary outcome measurements in assessing insulin sensitivity/resistance in clinical studies of Asian Indians.
    AJP Endocrinology and Metabolism 10/2010; 299(6):E1106-12. · 4.51 Impact Factor
  • Ranganath Muniyappa
    Hypertension 12/2009; 55(2):e13. · 6.87 Impact Factor
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    ABSTRACT: After a constant insulin infusion is initiated, determination of steady-state conditions for glucose infusion rates (GIR) typically requires >or=3 h. The glucose infusion follows a simple time-dependent rise, reaching a plateau at steady state. We hypothesized that nonlinear fitting of abbreviated data sets consisting of only the early portion of the clamp study can provide accurate estimates of steady-state GIR. Data sets from two independent laboratories were used to develop and validate this approach. Accuracy of the predicted steady-state GDR was assessed using regression analysis and Altman-Bland plots, and precision was compared by applying a calibration model. In the development data set (n = 88 glucose clamp studies), fitting the full data set with a simple monoexponential model predicted reference GDR values with good accuracy (difference between the 2 methods -0.37 mg x kg(-1) x min(-1)) and precision [root mean square error (RMSE) = 1.11], validating the modeling procedure. Fitting data from the first 180 or 120 min predicted final GDRs with comparable accuracy but with progressively reduced precision [fitGDR-180 RMSE = 1.27 (P = NS vs. fitGDR-full); fitGDR-120 RMSE = 1.56 (P < 0.001)]. Similar results were obtained with the validation data set (n = 183 glucose clamp studies), confirming the generalizability of this approach. The modeling approach also derives kinetic parameters that are not available from standard approaches to clamp data analysis. We conclude that fitting a monoexponential curve to abbreviated clamp data produces steady-state GDR values that accurately predict the GDR values obtained from the full data sets, albeit with reduced precision. This approach may help reduce the resources required for undertaking clamp studies.
    AJP Endocrinology and Metabolism 11/2009; 298(2):E229-36. · 4.51 Impact Factor
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    ABSTRACT: Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34-0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome.
    AJP Endocrinology and Metabolism 09/2009; 297(5):E1023-9. · 4.51 Impact Factor
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    ABSTRACT: Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance. Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium. The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure, improve endothelial dysfunction, and ameliorate insulin resistance in subjects with essential hypertension. We conducted a randomized, placebo-controlled, double-blind, crossover trial of a flavanol-rich cocoa drink (150 mL twice a day, approximately 900 mg flavanols/d) in individuals with essential hypertension (n = 20). Antihypertensive medications were discontinued before study enrollment. After a 7-d cocoa-free run-in period, cocoa or flavanol-poor placebo (approximately 28 mg flavanols/d) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm. Blood pressure was measured thrice weekly. At baseline and after each treatment period, we assessed insulin sensitivity (hyperinsulinemic-isoglycemic glucose clamp) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment (Doppler ultrasound with or without microbubble contrast). Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [median percentage increase from baseline (25th-75th percentile): 8.3 (4.2-11.3) compared with 5.9 (-0.3 to 9.6); P < 0.04]. Nevertheless, cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment, circulating plasma concentrations of adipocytokines, or endothelial adhesion molecules. Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension. This trial was registered at clinicaltrials.gov as NCT00099476.
    American Journal of Clinical Nutrition 01/2009; 88(6):1685-96. · 6.50 Impact Factor
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    Ranganath Muniyappa, Micaela Iantorno, Michael J Quon
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    ABSTRACT: Endothelial dysfunction and insulin resistance are frequently comorbid states. Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways that stimulate production of nitric oxide from vascular endothelium. This helps to couple metabolic and hemodynamic homeostasis under healthy conditions. In pathologic states, shared causal factors, including glucotoxicity, lipotoxicity, and inflammation selectively impair PI3K-dependent insulin signaling pathways that contribute to reciprocal relationships between insulin resistance and endothelial dysfunction. This article discusses the implications of pathway-selective insulin resistance in vascular endothelium, interactions between endothelial dysfunction and insulin resistance, and therapeutic interventions that may simultaneously improve both metabolic and cardiovascular physiology in insulin-resistant conditions.
    Endocrinology & Metabolism Clinics of North America 10/2008; 37(3):685-711, ix-x. · 3.79 Impact Factor

Publication Stats

1k Citations
188.33 Total Impact Points

Institutions

  • 2011–2013
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States
    • St Joseph Medical Center (MD, USA)
      Maryland, United States
    • University of Rome Tor Vergata
      • Dipartimento di Medicina dei Sistemi
      Roma, Latium, Italy
  • 2006–2013
    • National Institutes of Health
      • • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      • • Office of Cancer Complementary and Alternative Medicine
      Bethesda, MD, United States
  • 2007
    • University of Missouri
      • Department of Internal Medicine
      Columbia, MO, United States