Islet-1: a potentially important role for an islet cell gene in visceral fat.

Objective: To examine differences in gene expression between visceral (VF) and subcutaneous fat (SF) to identity genes of potential importance in regulation of VF.

Methods And Procedures: We compared gene expression (by DNA array and quantitative PCR (qPCR)) in paired VF and SF adipose biopsies from 36 subjects (age 54 +/- 15 years, 15 men/21 women) with varying degrees of adiposity and insulin resistance, in chow and fat fed mice (+/- rosiglitazone treatment) and in c-Cbl(-/-) mice. Gene expression was also examined in 3T3-L1 preadipocytes during differentiation.

Serum adiponectin levels in normal and hypertensive pregnancy.

Objective: The aim of this study was to quantify adiponectin levels in women with normal and hypertensive pregnancies to determine whether there is an independent association, while controlling for body fat and insulin sensitivity.

Methods: A cross-sectional study was conducted in the following categories: 12 normotensive non-pregnant women, 10 normotensive, 12 gestational hypertensive, 13 essential hypertensive, and 12 preeclamptic women. All subjects underwent measurements of body fat by bio-impedance analysis and blood sampling.

Insulin resistance does not influence gene expression in skeletal muscle.

Insulin resistance is commonly observed in patients prior to the development of type 2 diabetes and may predict the onset of the disease. We tested the hypothesis that impairment in insulin stimulated glucose-disposal in insulin resistant patients would be reflected in the gene expression profile of skeletal muscle. We performed gene expression profiling on skeletal muscle of insulin resistant and insulin sensitive subjects using microarrays.

Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability.

Objective: To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability.

Research Methods And Procedures: We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic-euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL; by 1H-magnetic resonance spectroscopy). Our cohort included normal weight to obese men (n = 36).

The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals.

Objective: Little is known of the metabolism of different isoforms of adiponectin. We therefore (a) characterised the size distribution of human adiponectin in relation to gender, body composition and following a challenge with a fat meal or oral glucose in humans, and (b) studied the metabolism of isoforms of human adiponectin in rabbits.

Method: Electrophoresis, blotting and chromatography were used to characterise human adiponectin in 36 healthy subjects, including 15 with at least two first-degree relatives with type 2 diabetes, before and after consumption of a fatty meal or glucose.

Insulin resistance and postprandial triglyceride levels in primary renal disease.

Background: Renal failure is associated with a range of metabolic abnormalities including insulin resistance and dyslipidemia. We examined the role of creatinine clearance (CrCl) and body composition in the development of insulin resistance in patients with primary renal disease and a variable degree of renal failure. We also determined the effect of a high-fat meal on postprandial triglyceride levels in a subgroup of these patients.

Inflammation, insulin resistance, and adiposity: a study of first-degree relatives of type 2 diabetic subjects.

Objective: Inflammatory markers such as C-reactive protein (CRP) are associated with insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains unresolved. We aimed to determine whether first-degree relatives of type 2 diabetic subjects differ in insulin sensitivity from control subjects without a family history of diabetes, whether first-degree relatives of type 2 diabetic subjects and control subjects differ in CRP, adiponectin, and complement levels, and whether CRP is related to insulin sensitivity independently of adiposity.

Insulin action, regional fat, and myocyte lipid: altered relationships with increased adiposity.

Objective: Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity.

Research Methods And Procedures: Myocyte triglyceride content ((1)H-magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.

Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status.

We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TG(m)) concentration, fatty acid transporter protein content, and oxidative enzyme activity in eight patients with type 2 diabetes (TYPE 2); six healthy control subjects matched for age (OLD), body mass index, percentage of body fat, and maximum pulmonary O(2) uptake; nine well-trained athletes (TRAINED); and four age-matched controls (YOUNG). Muscle biopsies from the vastus lateralis were taken before and after a 2-h euglycemic-hyperinsulinemic clamp. Oxidative enzyme activities, fatty acid transporters (FAT/CD36 and FABPpm), and TG(m) were measured from basal muscle samples, and total LCACoA content was determined before and after insulin stimulation.

Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content.

Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL).

Changes in aerobic capacity and visceral fat but not myocyte lipid levels predict increased insulin action after exercise in overweight and obese men.

Objective: To examine the effect of moderate intensity physical activity on the interactions between central abdominal adiposity, myocyte lipid content, and insulin action in overweight and obese, sedentary men.

Research Design And Methods: Myocyte lipid (biochemical triglyceride and long-chain acyl CoA [LCAC] from vastus lateralis biopsy and soleus and tibialis anterior intramyocellular lipid by (1)H-magnetic resonance spectroscopy), regional body and abdominal fat (dual-energy X-ray absorptiometry and magnetic resonance imaging), serum lipids, insulin action (hyperinsulinemic-euglycemic clamp), and substrate oxidation were measured in 18 nondiabetic, sedentary, and overweight to obese men (aged 37.4 +/- 1.

Multiple indexes of lipid availability are independently related to whole body insulin action in healthy humans.

An increase in muscle lipid content has been postulated to relate closely to the evolution of insulin resistance. We aimed to test whether the multiple indexes of lipid supply within man [namely, circulating triglycerides, skeletal muscle triglycerides (SMT), total and central fat mass, and circulating leptin] were independent predictors of insulin resistance, or whether triglycerides from different sources are additive in their influence on whole body insulin sensitivity. Whole body insulin sensitivity, body composition, and SMT content were determined in 49 sedentary, nondiabetic males (age, 20-74 yr; body mass index, 20-38 kg/m(2)).

Body fatness, insulin sensitivity and muscle oxygen supply in adolescents.

Muscle blood flow can be reduced in insulin-resistant states. The present study examined the importance of body fatness and insulin sensitivity as variables that may be associated with muscle oxygen supply. We studied 38 adolescents (22 males, 16 females; age 15.