Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men

South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians.Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27+/-3 and 27+/-3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size.Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22+/-6 and 15+/-4% of body weight; p-value<0.0001), higher SA fat (3.5+/-1.9 and 2.2+/-1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0+/-0.5 and 1.0+/-0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491+/-1393 and 1648+/-864 microm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = -0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = -0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians.Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat

Liraglutide Reduces Oxidative Stress And Restores Heme Oxygenase-1 and Ghrelin Levels in Patients with Type 2 Diabetes: A Prospective Pilot Study

Context: Liraglutide is a glucagon-like peptide-1 analog and glucose-lowering agent whose effects on cardiovascular risk markers have not been fully elucidated. Objective: We evaluated the effect of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes mellitus (T2DM). Design and Setting: A prospective pilot study of 2 months duration has been performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): Twenty subjects with T2DM (10 men and 10 women; meanage: 57 +/- 13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d) in addition to metformin (1500 mg/d orally) for 2 months. Patients with liver disorders or renal failure were excluded. Main Outcome Measure(s): Plasma ghrelin concentrations, oxidative stress markers, and heat-shock proteins, including HO-1 were assessed. Results: The addition of liraglutide resulted in a significant decrease in glycated hemoglobin (HbA1c) (8.5 +/- 0.4 vs 7.5 +/- 0.4%, P LT .0001). In addition, plasma ghrelin and glutathione concentrations increased (8.2 +/- 4.1 vs 13.6 +/- 7.3 pg/ml, P = .0007 and 0.36 +/- 0.06 vs 0.44 +/- 0.07 nmol/ml, P = .0002, respectively), whereas serum lipid hydroperoxides and HO-1 decreased (0.11 +/- 0.05 vs 0.04 +/- 0.07 pg/ml, P = .0487 and 7.7 +/- 7.7 vs 3.6 +/- 1.8 pg/ml, P = .0445, respectively). These changes were not correlated with changes in fasting glycemia or HbA1c. Conclusions: In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM. These findings seemed to be independent of the known effects of liraglutide on glucose metabolism

Role of ENPP1 on Adipocyte Maturation

BACKGROUND: It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over-expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over-expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. CONCLUSIONS: We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity

Role of ENPP1 on Adipocyte Maturation

Background. It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over-expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. Methodology/Principal Findings. ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over-expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. Conclusions. We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity

Ethnic difference in sex gap in high-density lipoprotein cholesterol between Asian Indians and Whites

Objective: To study whether low plasma high-density lipoprotein cholesterol (HDL-C) reported in Asian Indians is common in both men and women when compared with whites and whether it is related to increased body mass index (BMI) and plasma triglyceride concentration. Design: We evaluated the lipid profile and prevalence of low HDL-C (&lt;40 mg/dL in men and &lt;50 mg/dL in women) in the following cohorts of normoglycemic 1404 men and 1817 women: Asian Indians living in rural India; urban Chennai, India; and Dallas, TX; and whites living in Dallas, TX. Results: After adjustment for age, BMI, and smoking, HDL-C was not significantly different in Asian Indian men compared with whites. However, Asian Indian women had lower HDL-C compared with white women, and rural Asian Indian women had the lowest HDL-C even in the absence of high triglycerides. Lean Asian Indian women with BMI of less than 23 kg/m2 had higher frequency of low HDL-C compared with lean white women with BMI of less than 25 kg/m2 (72%, 56%, 48%, and 25% in rural, urban, and Dallas Asian Indian and white women, respectively) and lean men (52%, 42%, 28%, and 35% in rural, urban, and Dallas Asian Indian and white men, respectively). Sex differences in HDL-C was estimated as 6.6 &#177; 0.5 mg/dL for Asian Indians and 15.3 &#177; 1.1 mg/dL for whites (P &lt; 0.0001 for sex difference in the 2 ethnic groups). Conclusions: Increased prevalence of low HDL-C independently of obesity or hypertriglyceridemia is observed in women but not in men of Asian Indian origin. The sex gap in HDL-C is significantly smaller in Asian Indians compared with whites independent of geographical location

Human ENPP1 over-expression inhibits DMI-induced adipocyte maturation in 3T3-L1 cells.

<p>Human ENPP1 was over-expressed in 3T3-L1 using retrovirus transfection with CMV promoter. Panel A. ENPP1 protein content in cells containing vector only and in cells over-expressing human ENPP1 K121K or K121Q. ENPP1 was identified at 130 kDa using antibody from Imegex Corp. (San Diego, CA). Panel B. Oil-red-O stained 3T3-L1 cells after induction of adipogenesis. Cells were 100% confluent at the time of assay. Cellular triglyceride content is presented as fold changes from the triglyceride content of cells containing vector. Results are reported as mean and SD from measurements performed three times (8 wells measured in each experiment). Panel C. Cells were plated on 6-well plate and induced to differentiation with DMI. At different days, as indicated, the cell number was counted. Results are reported as mean and SD from measurements repeated three times (3 wells measured in each experiment). Open squares represent the data for the vector 3T3-L1. Open circles represent the data for 3T3-L1 over-expressing human ENPP1 K121K. Dark circles represent the data for 3T3-L1 over-expressing human ENPP1 K121Q. Cell death was measured at day 2 and day 4 of differentiation with DMI. Results are shown as mean and SD of percentage of dead cells relative to total cells. Measurements were performed for number of viable and dead cells in three wells for each cell type. These experiments were repeated 3 times. * p<0.05 for t-test between 3T3-L1 over-expressing human ENPP1 K121K and the vector group. † p<0.05 for t-test between 3T3-L1 over-expressing human ENPP1 K121Q and the vector group.</p