Metabolism - Clinical and Experimental

Masthead

2012-05-01

Can the sunshine vitamin melt the fat?

Ghada El-Hajj Fuleihan — 2012-02-10

Noncommunicable diseases (NCDs), namely, cardiovascular diseases, diabetes, obesity, cancer, and chronic respiratory diseases, were identified by the World Health Organization as the leading cause of death, accounting for two thirds of all causes of deaths worldwide . These diseases are projected to further increase in view of global urbanization, sedentary lifestyle, and increased life expectancy in populations across the globe. Abdominal obesity, hyperglycemia, dyslipidemia, and hypertension, core traits of the metabolic syndrome (MetS) phenotype, account in large part for the rising tide in these NCDs . The prevalence of MetS has swiftly risen from 22% in 1988-1994 to 34.5% in 1999-2002 in the United States National Health and Nutrition Examination Survey . Similar trends are noted worldwide in general and in the Middle East in particular, where obesity rates in some countries reach 40% to 70%, exceeding those in Western countries . This region also registers the greatest relative increase in diabetes prevalence, with rates reaching 20% in Bahrain, Saudi Arabia, and the United Arab Emirates .

Metabolic consequences of stress during childhood and adolescence

Panagiota Pervanidou, George P. Chrousos — 2011-12-07

Abstract: Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity-related health problems.

Long-term recovery of β-cell function after partial pancreatectomy in humans

2011-11-14

Abstract: Glucose homeostasis is significantly altered immediately after partial pancreatectomy. The present study examined the long-term consequences of a hemipancreatectomy in 10 patients with chronic pancreatitis and 10 patients with benign pancreatic and extrapancreatic tumors. A 240-minute oral glucose challenge was performed before and shortly after pancreatic surgery, as well as after a follow-up of 3.1 ± 0.5 years. Plasma concentrations of glucose, insulin, and C-peptide were determined; and indices of insulin sensitivity and insulin secretion were calculated. In both groups of patients, fasting and postchallenge glucose concentrations were significantly altered immediately after surgery, but returned to preoperative levels at the time of follow-up (P < .0001). Postchallenge insulin and C-peptide concentrations were reduced immediately after surgery (P < .0001), but were partly normalized at the time of follow-up (P < .0001). These changes were not accompanied by improvements in insulin sensitivity (Matsuda index). However, the oral disposition index revealed a significant recovery of β-cell function at the time of follow-up (P < .05). These findings demonstrate a capacity for recovery of glucose control after partial pancreatectomy and suggest that β-cell function can improve significantly over time even in adult humans.

ENPP1 K121Q polymorphism and type 2 diabetes mellitus in the Chinese population: a meta-analysis including 11 855 subjects

Yan-yan Li — 2011-12-05

Abstract: Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) K121Q gene polymorphism has been suggested to be associated with the increased risk of developing type 2 diabetes mellitus (T2D), but relevant research results are still contradictory. To explore the relationship between ENPP1 K121Q gene polymorphism and T2D in the Chinese population, a meta-analysis was performed. Fourteen independent studies involving 11 855 subjects were retrieved from electronic databases. The pooled odds ratio (ORs) for the distribution of Q allele frequency of the ENPP1 K121Q gene and its corresponding 95% confidence interval (95% CI) were assessed using a random-effects model. Under an allelic model of inheritance, the distribution of Q allele frequency was 0.107 for the T2D group and 0.093 for the control group. The pooled OR for the distribution of Q allele frequency of ENPP1 K121Q gene was 1.29 (95% CI, 1.09-1.53; Pheterogeneity = .006; I2 = 55.6%). There was a significant association between ENPP1 K121Q gene polymorphism and T2D in the Chinese population (P = .003). Under a dominant model of inheritance, the KQ + QQ/KK value was 0.259 for the T2D group and 0.220 for the control group. The pooled OR for the KQ + QQ/KK value was 1.51 (95% CI, 1.20-1.91; Pheterogeneity < .0001; I2 = 71.8%). The association between ENPP1 K121Q gene polymorphism and T2D in the Chinese population followed a dominant model of inheritance (P = .0005). In the Chinese population, the ENPP1 K121Q gene polymorphism was implied to be involved with T2D susceptibility. People with the Q allele of the ENPP1 K121Q gene might be predisposed to T2D.

Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women

2011-11-10

Abstract: Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (SI) among African Americans (AA) compared with European Americans (EA). Whole-body SI represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic SI. The purpose of this study was to examine specific indexes of SI among AA and EA women to determine whether lower whole-body SI in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal SI and Hepatic SI were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6-2H2]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal SI and Hepatic SI were lower among AA (P = .009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole-body SI among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic SI, AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk.

Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects

2011-12-07

Abstract: It is unclear whether high-fructose corn syrup (HFCS), which contains a higher amount of fructose and provides an immediate source of free fructose, induces greater systemic concentrations of fructose as compared with sucrose. It is also unclear whether exposure to higher levels of fructose leads to increased fructose-induced adverse effects. The objective was to prospectively compare the effects of HFCS- vs sucrose-sweetened soft drinks on acute metabolic and hemodynamic effects. Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened beverages in a randomized crossover design study. Blood and urine samples were collected over 6 hours. Blood pressure, heart rate, fructose, and a variety of other metabolic biomarkers were measured. Fructose area under the curve and maximum concentration, dose-normalized glucose area under the curve and maximum concentration, relative bioavailability of glucose, changes in postprandial concentrations of serum uric acid, and systolic blood pressure maximum levels were higher when HFCS-sweetened beverages were consumed as compared with sucrose-sweetened beverages. Compared with sucrose, HFCS leads to greater fructose systemic exposure and significantly different acute metabolic effects.

Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus

2011-11-14

Abstract: Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M-values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin-mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS.

Modest reversal of metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study

2011-11-10

Abstract: Numerous cross-sectional studies have noted significant negative associations between circulating levels of 25-hydroxyvitamin D and cardiometabolic risk factors, highlighting potential extraskeletal functions of this sterol hormone. Prospective studies, however, have been limited; and hence, no cause-and-effect relations can be inferred. This study aims to determine whether vitamin D status correction can reverse already established manifestations of the metabolic syndrome (MetS). A total of 59 adult nondiabetic, overweight, and obese Saudis (31 male, 28 female) were prospectively enrolled in this 1-year interventional study. Anthropometry and biochemical evaluation were performed, including determination of serum 25-hydroxyvitamin D, calcium, and phosphorous concentrations, as well as fasting blood glucose and lipid profile. Subjects were advised to regularly expose themselves to sunlight and increase intake of vitamin D–rich foods. All measurements were repeated 6 and 12 months later. At the initial baseline visit, the prevalence of both low high-density lipoprotein cholesterol and hypertension was significantly increased among patients with 25-vitamin D deficiency (P < .05), even after adjusting for sex and body mass index. Overall prevalence of MetS patients by the modified National Health and Nutrition Examination Survey Adult Treatment Panel III definition decreased from 25.2% to 13.0%; and this was largely due to a parallel decrease in the prevalence of low high-density lipoprotein cholesterol, triglycerides, and hypertension. Optimization of vitamin D status through sun exposure and increased intake of a vitamin D–rich diet can lead to an improved cardiometabolic profile, offering a promising nonpharmacologic approach in the prevention of MetS manifestations.

Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance

2011-11-10

Abstract: Insulin resistance (IR) is a complex disorder caused by an interplay of both genetic and environmental factors. Recent studies identified a significant interaction between body mass index (BMI) and the rs1800795 polymorphism of the interleukin-6 gene that influences both IR and onset of type 2 diabetes mellitus, with obese individuals homozygous for the C allele demonstrating the highest level of IR and greatest risk for type 2 diabetes mellitus. Replication of a gene-environment interaction is important to confirm the validity of the initial finding and extend the generalizability of the results to other populations. Thus, the objective of this study was to replicate this gene-environment interaction on IR in a hypertensive population and perform a meta-analysis with prior published results. The replication analysis was performed using white individuals with hypertension from the Hypertensive Pathotype cohort (N = 311), genotyped for rs1800795. Phenotype studies were conducted after participants consumed 2 diets—high sodium (200 mmol/d) and low sodium (10 mmol/d)—for 7 days each. Measurements for plasma glucose, insulin, and interleukin-6 were obtained after 8 hours of fasting. Insulin resistance was characterized by the homeostatic model assessment (HOMA-IR). In Hypertensive Pathotype, BMI was a significant effect modifier of the relationship between rs1800795 and HOMA-IR; higher BMI was associated with higher HOMA-IR among homozygote CC individuals when compared with major allele G carriers (P = .003). Furthermore, the meta-analysis in 1028 individuals confirmed the result, demonstrating the same significant interaction between rs1800795 and BMI on HOMA-IR (P = 1.05 × 10−6). This rare replication of a gene-environment interaction extends the generalizability of the results to hypertension while highlighting this polymorphism as a marker of IR in obese individuals.

Change of energy expenditure from physical activity is the most powerful determinant of improved insulin sensitivity in overweight patients with coronary artery disease participating in an intensive lifestyle modification program

2011-12-07

Abstract: The objective was to evaluate the determinants of change (Δ) in insulin sensitivity in overweight coronary artery disease male patients without diabetes after an intensive lifestyle intervention. All patients received nutritional counseling and performed 4 months of exercise training (ET) according to 1 of 2 protocols: aerobic ET (65%-70% of peak aerobic capacity [VO2]) 25 to 40 minutes 3 times a week (n = 30) or walking (50%-60% of peak VO2) 45 to 60 minutes at least 5 times a week (n = 30). Data from participants of both ET groups were pooled, and post–intensive lifestyle intervention results were compared with baseline data. The primary outcome was Δ insulin sensitivity (m-value) assessed by the criterion standard technique, the euglycemic-hyperinsulinemic clamp. Changes in weight, body mass index, total and percentage fat mass (by dual-energy x-ray absorptiometry scan), waist circumference, total abdominal and visceral fat (by computed tomographic scan), high-sensitivity C-reactive protein, peak VO2, daily energy intake, and physical activity energy expenditure (PAEE) (by doubly labeled water technique) were also assessed. Daily energy intake decreased by 335 kcal, and PAEE increased by 482 kcal/d (all P < .0001). The mean weight loss was 6.4 kg, and the mean improvement in m-value was 1.6 mg/kg fat-free mass per minute. Univariate determinants of Δ m-value were low baseline PAEE, walking protocol, Δ weight, Δ body mass index, Δ total and percentage fat mass, Δ waist circumference, Δ total abdominal and visceral fat, and Δ PAEE (all P < .05). In multivariate analysis, the only significant determinant of Δ m-value was Δ PAEE (P < .02). In this analysis, the most powerful determinant of improved insulin sensitivity in overweight coronary artery disease patients is the change in PAEE.

In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric dimethylarginine in obese subjects without and with metabolic syndrome

Mario Siervo, Les J.C. Bluck — 2011-12-07

Abstract: Metabolic syndrome (MetSyn) is associated with impaired endothelial function. Here the association between nitric oxide (NO) production and insulin sensitivity (Si) in obese subjects with and without MetSyn was evaluated. The relationship between NO production and asymmetric dimethylarginine (ADMA) was also explored. Seven healthy normal-weight subjects (male/female [M/F], 3/4; age, 27.4 ± 10.9 years; body mass index [BMI], 21.9 ± 2.2 kg/m2), 7 obese subjects without MetSyn (M/F, 1/6; age, 48.0 ± 8.0 years; BMI, 34.5 ± 2.3 kg/m2), and 7 with MetSyn (M/F, 3/4; age, 48.0 ± 10.7 years; BMI, 33.4 ± 2.9 kg/m2) were recruited. Body composition and cardiometabolic functions (blood pressure, glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein, ADMA) were measured. A frequent sampling intravenous glucose tolerance test was performed to measure Si. A novel stable isotopic method was used to measure in vivo rates of NO production. The NO production was lower in obese subjects with MetSyn compared with normal-weight subjects and obese subjects without MetSyn. Similarly, Si was significantly lower in obesity, both without and with MetSyn, compared with the control group. A significant direct association was found between NO synthesis and Si (ρ = 0.47, P = .03). Circulating levels of ADMA were significantly higher in the obese group with MetSyn. A nonsignificant negative trend between ADMA and NO synthesis was observed. The association between Si and NO production suggests a close mechanistic link between endothelial function and insulin signaling. The results may be highly informative for the development of controlled longitudinal interventions to improve endothelial and metabolic regulation.

Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women

Andréanne Michaud, Renée Drolet, Suzanne Noël, Gaëtan Paris, André Tchernof — 2011-12-09

Abstract: We tested the hypothesis that visceral obesity is the best correlate of abdominal adipose tissue macrophage infiltration in women. Omental and subcutaneous fat samples were surgically obtained from 40 women (age, 47.0 ± 4.0 years; body mass index, 28.4 ± 5.8 kg/m2). CD68+ cells were identified using fluorescence immunohistochemistry. Expression of macrophage markers was measured by real-time reverse transcriptase polymerase chain reaction. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography, respectively. Mean CD68+ cell percentage tended to be higher in subcutaneous (18.3%) compared with omental adipose tissue (15.5%, P = .07). Positive correlations were observed between CD68+ cell percentage as well as CD68 messenger RNA expression in a given depot vs the other (P ≤ .01). Visceral adipose tissue area and omental adipocyte diameter were positively related to CD68+ cell percentage in omental fat (r = 0.52 and r = 0.35, P ≤ .05). Total and visceral adipose tissue areas as well as subcutaneous adipocyte diameter were significantly correlated with CD68+ cell percentage in subcutaneous adipose tissue (0.32 ≤ r ≤ 0.40, P ≤ .05). Adipose tissue areas and subcutaneous adipocyte diameter were also significantly associated with expression of commonly used macrophage markers including CD68 in the subcutaneous fat compartment (0.32 ≤ r ≤ 0.57, P ≤ .05). Visceral adipose tissue area was the best correlate of CD68+ cell percentage in both omental and subcutaneous fat tissues, explaining, respectively, 20% and 12% of the variance in models also including subcutaneous adipose tissue area, adipocyte sizes, and total body fat mass. Visceral adipose tissue accumulation is the best correlate of macrophage infiltration in both the subcutaneous and omental fat compartments of lean to obese women.

Maternal serum resistin at 11 to 13 weeks' gestation in normal and pathological pregnancies

2011-12-07

Abstract: The objective was to examine maternal serum levels of resistin at 11 to 13 weeks' gestation in normal and pathological pregnancies. Serum resistin, pregnancy-associated plasma protein A (PAPP-A), and uterine artery pulsatility index (PI) at 11 to 13 weeks were measured in 480 singleton pregnancies, including 240 with normal outcome, 60 that subsequently developed preeclampsia (PE), 60 that developed gestational diabetes mellitus (GDM), 60 that delivered large for gestational age (LGA) neonates, and 60 that delivered small for gestational age (SGA) neonates. Each value in both the normal and pathological outcome groups was expressed as a multiple of the expected normal median (MoM), and the median MoM values in the outcome groups were compared. In the PE group, compared with the controls, there were an increase in median resistin (1.22 MoM, P = .003) and uterine artery PI (1.25 MoM, P < .0001) and a decrease in serum PAPP-A (0.72, P < .0001). There was no significant association between serum resistin with either uterine artery PI (P = .415) or serum PAPP-A (P = .290). In the SGA, LGA, and GDM groups, serum resistin MoM was not significantly different from that of the controls (P = .415, P = .702, and P = .549, respectively). In pregnancies that develop PE, maternal serum resistin concentration at 11 to 13 weeks is increased in a manner not related to altered placental perfusion or function. In pregnancies complicated by the development of GDM or delivery of SGA or LGA neonates, serum resistin is not significantly altered.

Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity

2011-12-05

Abstract: Chemerin is a chemoattractant adipokine that regulates adipogenesis and may induce insulin resistance. Chemerin serum concentrations are elevated in obese, insulin-resistant, and inflammatory states in vivo. Here we investigate the role of omental (OM) and subcutaneous (SC) adipose tissue chemerin and CMKLR1 messenger RNA (mRNA) expression in human obesity. In addition, we test the hypothesis that changes in chemerin serum concentrations are primarily associated with reduced body fat mass in the context of 3 weight loss intervention studies. Chemerin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which OM and SC chemerin mRNA expression has been analyzed as well as in 3 interventions including 12 weeks of exercise (n = 60), 6 months of calorie-restricted diet (n = 19) studies, and 12 months after bariatric surgery (n = 32). Chemerin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes mellitus and correlates with circulating chemerin, body mass index (BMI), percentage body fat, C-reactive protein, homeostasis model assessment of insulin resistance, and glucose infusion rate in euglycemic-hyperinsulinemic clamps. CMKLR1 mRNA expression was not significantly different between the 2 fat depots. Obesity surgery–induced weight loss causes a significant reduction on both OM and SC chemerin expression. All interventions led to significantly reduced chemerin serum concentrations. Decreased chemerin serum concentrations significantly correlate with improved glucose infusion rate and reduced C-reactive protein levels independently of changes in BMI. Insulin resistance and inflammation are BMI-independent predictors of elevated chemerin serum concentrations. Reduced chemerin expression and serum concentration may contribute to improved insulin sensitivity and subclinical inflammation beyond significant weight loss.

Prediction of gestational diabetes mellitus at 24 to 28 weeks of gestation by using first-trimester insulin sensitivity indices in Asian Indian subjects

2011-12-07

Abstract: The aim of the present study was to predict the development of gestational diabetes mellitus (GDM) after 24 weeks of gestation by using first-trimester insulin indices. A total of 298 nondiabetic pregnant women underwent 3-hour oral glucose tolerance test (OGTT) in the first trimester of pregnancy. The normoglycemic women underwent second OGTT between 24 and 28 weeks. Insulin sensitivity and resistance indices were calculated by using the Matsuda index (composite insulin sensitivity from OGTT), quantitative insulin sensitivity check index, and homeostasis model assessment for insulin resistance and sensitivity by using the results of the first-trimester OGTT. These indices were compared between subjects who were diagnosed as having GDM and subjects with normal glucose tolerance in the second OGTT. The overall prevalence of GDM was 15.49% (24 in the first trimester and 16 between 24 and 28 weeks). First-trimester fasting plasma insulin greater than 7.45 μU/mL was able to predict GDM with sensitivity and specificity of 80% and 57.4%, respectively. The negative predictive value for this parameter was 0.97. Values of first-trimester composite insulin sensitivity from OGTT less than 5.5 had sensitivity and specificity of 71.4% and 62.5% for the prediction of GDM. First-trimester hyperinsulinemia preceded the onset of hyperglycemia between 24 and 28 weeks of gestation and would predict the development of GDM with limited sensitivity and specificity.

Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation

2011-11-11

Abstract: We herein studied the role of glutamate dehydrogenase (GDH), in response to leucine (LEU) supplementation, upon insulin secretion of malnourished rats. Weaned male Wistar rats were fed normal-protein (17%) or low-protein diet (6%, LP) for 8 weeks. Half of the rats of each group were supplemented with LEU (1.5%) in the drinking water for the following 4 weeks. Gene and protein expressions, static insulin secretion, and cytoplasmic Ca2+ oscillations were measured. Glutamate dehydrogenase messenger RNA was 58% lower in LP islets, and LEU supplementation augmented it in 28%. The LP islets secreted less insulin when exposed to 20 mmol/L LEU, 20 mmol/L LEU + 2 mmol/L glutamine (with or without 5 mmol/L aminooxyacetic acid, a branched chain aminotransferase inhibitor, or 20 μmol/L epigallocatechin gallate, a GDH inhibitor), 20 mmol/L α-ketoisocaproate, glutamine + 20 mmol/L β-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (a GDH activator), and 22.2 mmol/L glucose. Leucine supplementation augmented insulin secretion to levels found in normal-protein islets in all the above conditions, an effect that was blunted when islets were incubated with epigallocatechin gallate. The glutamine + β-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid–induced increased [Ca2+]i and oscillations were higher than those for LP islets. Leucine supplementation normalized these parameters in LP islets. Impaired GDH function was associated with lower insulin release in LP islets, and LEU supplementation normalized insulin secretion via restoration of GDH function. In addition, GDH may contribute to insulin secretion through ameliorations of Ca2+ handling in LP islets.

In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase–independent manner

Brendon J. Gurd, Graham P. Holloway, Yuko Yoshida, Arend Bonen — 2011-11-11

Abstract: In selected cell lines, it appears (a) that metabolic stressors induce the translocation of SIRT3 from the nucleus to mitochondria and (b) that SIRT3 may contribute to the regulation of mitochondrial biogenesis and/or fatty acid utilization. We have examined in mammalian muscle (1) the association between SIRT3 protein content and muscle oxidative capacity and mitochondrial fatty acid oxidation, (2) the subcellular location of SIRT3, (3) whether exercise induces the translocation of SIRT3 from the nucleus to the mitochondria, and (4) the response of SIRT3 protein to stressors known to induce mitochondrial biogenesis (chronic muscle stimulation and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside administration). SIRT3 protein displayed hierarchical expression based on oxidative potential of muscle tissues (heart >> red >> white). In contrast to studies in some cell lines, metabolic stress (exercise) did not induce the translocation of SIRT3 from the nucleus to mitochondria, as SIRT3 was only present in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, not in the nucleus. Chronic stimulation increased muscle mitochondrial content and SIRT3 protein in SS (+33%) and IMF (+27%) mitochondria (P < .05). In contrast, chronic 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside administration, while inducing mitochondrial biogenesis, did not alter SS or IMF mitochondrial SIRT3 protein content. These studies have shown that, in muscle, SIRT3 (a) scales with muscle oxidative capacity and with enzymes regulating fatty acid oxidation, (b) in resting muscle is localized to SS and IMF mitochondria and not nuclei, (c) in contracting muscle is not acutely translocated to mitochondria, and (d) is upregulated with chronic stimulation in an adenosine monophosphate–activated protein kinase–independent manner.

A tea/vanadate decoction delivered orally over 14 months to diabetic rats induces long-term glycemic stability without organ toxicity

2011-12-07

Abstract: Vanadium can induce potent hypoglycemic effects in type 1 and type 2 diabetes mellitus animals, but toxic adverse effects have inhibited the translation of these findings. Administration of vanadate in a black tea decoction has shown impressive hypoglycemic effects without evidence of toxicity in short-term studies. The purpose of this study was to investigate the hypoglycemic action and the toxic adverse effects of a tea/vanadate (T/V) decoction in diabetic rats over a 14-month treatment period. Streptozotocin-induced type 1 diabetes mellitus rats were orally gavaged with 40 mg sodium vanadate in a black tea decoction only when blood glucose levels were greater than 10 mmol/L. Glycemic status and liver and kidney function were monitored over 14 months. All of the diabetic rats in this treatment group (n = 25) required treatment with the T/V decoction at the start of the study to reduce blood glucose levels to less than 10 mmol/L. Diarrhea was uncommon among the T/V-treated animals during the first week of T/V treatment and was absent thereafter. There was no evidence of liver or kidney dysfunction or injury. From 2 to 6 months, fewer animals required the T/V treatment to maintain their blood glucose levels. After 9 months of treatment, none of the diabetic animals required any T/V to maintain their blood glucose levels at less than 10 mmol/L. Oral administration of a T/V decoction provides safe, long-acting hypoglycemic effects in type 1 diabetes mellitus rats. The typical glycemic signs of diabetes were absent for the last 5 months of the study.

Stress during childhood and adolescence: how to combat?

Srijit Das — 2012-01-16

I read with much interest the published manuscript entitled “Metabolic consequences of stress during childhood and adolescence” by Pervanidou and Chrousos . The authors have rightly cited facts regarding the potential damage to cardiovascular, nervous, endocrine, and reproductive systems due to the ongoing stress in the critical period of life. I wish to share few scientific facts on this related topic.

Reply to: Stress during childhood and adolescence: How to combat?

Panagiota Pervanidou, George P. Chrousos — 2012-03-05

We thank Professor Srijit Das for his letter to the Editor entitled “Stress during childhood and adolescence: how to combat” regarding our recent article “Metabolic consequences of stress during childhood and adolescence” published in Metabolism. Professor Das shares his thoughts on the complex nature of pediatric stress, and expands the content of the article, by proposing intervention and prevention strategies to combat stress.

Editorial Board

2012-05-01

Metabolism - Clinical and Experimental

Masthead

Can the sunshine vitamin melt the fat?

Metabolic consequences of stress during childhood and adolescence

Long-term recovery of β-cell function after partial pancreatectomy in humans

ENPP1 K121Q polymorphism and type 2 diabetes mellitus in the Chinese population: a meta-analysis including 11 855 subjects

Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women

Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects

Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus

Modest reversal of metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study

Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance

Change of energy expenditure from physical activity is the most powerful determinant of improved insulin sensitivity in overweight patients with coronary artery disease participating in an intensive lifestyle modification program

In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric dimethylarginine in obese subjects without and with metabolic syndrome

Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women

Maternal serum resistin at 11 to 13 weeks' gestation in normal and pathological pregnancies

Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity

Prediction of gestational diabetes mellitus at 24 to 28 weeks of gestation by using first-trimester insulin sensitivity indices in Asian Indian subjects

Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation

In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase–independent manner

A tea/vanadate decoction delivered orally over 14 months to diabetic rats induces long-term glycemic stability without organ toxicity

Stress during childhood and adolescence: how to combat?

Reply to: Stress during childhood and adolescence: How to combat?

TOC

Editorial Board