Reduced oxidation of fat leading to a positive balance could be factor in the development obesity. Twenty-four-hour respiratory quotient (RQ) was measured 152 nondiabetic Pima Indians fed weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean SD); 93.9 22.9 kg; 32 9% fat]. RQ varied from 0.799 0.903. Prior change body weight, 24-h energy balance, sex, percent explained 18% variance (P less than 0.001). In subgroup 66 siblings 28 families, family membership 28% remaining 0.05)....

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare levels resistin, adiponectin leptin in lean obese subjects determine relationship between adipocytokines resistance. METHODS: We examined plasma 17 with a mean body mass index (BMI) approximately 23 34 non-diabetic individuals BMI 33. Insulin resistance assessed using homeostasis model assessment ratio (HOMA-R) formula...

Impaired glucose tolerance often presages the development of non-insulin-dependent diabetes mellitus. We have studied insulin action and secretion in 24 Pima Indians before after impaired 254 other subjects representing whole spectrum tolerance, including with overt diabetes. The transition from normal to was associated a decrease uptake during hyperinsulinemia, 0.018 0.016 mmol per minute (from 3.3 2.8 mg kilogram fat-free body mass minute) (P less than 0.0003). Mean plasma concentrations...

Insulin resistance and the concomitant compensatory hyperinsulinemia have been implicated in pathogenesis of hypertension. However, reports on relation between insulin blood pressure are inconsistent. This study was designed to investigate possibility racial differences this relation.

Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change unknown. We measured glucose disposal rates at submaximally- maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians followed their over 3.5 +/- 1.8 y (mean SD).(a) Insulin-resistant subjects gained less than insulin-sensitive (3.1 vs. 7.6 kg, P 0.0001). (b) The percent per year correlated...

Pima Indians have the highest reported prevalence rate of noninsulin-dependent diabetes mellitus (NIDDM) in world, so that metabolic comparisons with caucasians, who a much lower rate, should provide insights into pathogenesis NIDDM. We compared 81 Caucasians 211 Indian nondiabetic subjects similar age, sex, degree obesity, and glucose tolerance. During hyperinsulinemic euglycemic clamp at physiological insulin concentrations, were 17% more resistant than after accounting for any differences...

Bone morphology and function were studied in male spontaneously diabetic BB rats after 3–4 weeks of diabetes. The tibia lumbar vertebrae weights decreased, but the bone calcium percentage remained normal. volumes tibial metaphysis first vertebra normal on quantitative histomorphometry. Osteoclast, osteoblast, osteoid surface percentages, however, calculated daily mineral apposition rate (1.0 ± 0.4 vs. 5.6 0.6 μm/ day) (0.2 0.1 2.3 0.2 μm/day) all severely decreased rats. Plasma osteocalcin...

Insulin resistance in skeletal muscle may be an expression of the genetic basis a common form non-insulin-dependent diabetes mellitus (NIDDM) humans. Impaired insulin action results from apparent postreceptor defect signal transduction that limits influence hormone on various protein serine/threonine kinases and phosphatases are thought to contribute mechanism by which affects intracellular events. The fact numerous responses affected suggests cause involves early step action. Therefore, we...

If a single gene produced insulin resistance, with environmental effects creating some additional variance, action might be distributed as mixture of two normal distributions if the is dominant or recessive three codominant. To estimate maximal insulin-stimulated glucose uptake rates (MaxMs), hyperinsulinemic-euglycemic clamps were performed on 245 nondiabetic Pima Indians (126 men, 119 women). Five models (for 1, 2, 3, 4, 5 components each, normally common variance) fitted to frequency...

The influence of vitamin D status on insulin secretion and glucose tolerance was studied by a longitudinal design in the rabbit. Intravenous tests were performed Dutch rabbits (n = 12) before after nutritional deficiency, characterized an absence circulating 25-hydroxyvitamin D3, 50% decrease 1,25-dihydroxyvitamin 16% serum calcium concentrations. Glucose-induced reduced 41% as early 2 months start D-deficient diet associated with impairment tolerance. An iv infusion restored concentration...

Calcium homeostasis was investigated in male BB rats with a diabetes duration of 3–4 weeks and compared that nondiabetic littermates either fed ad libitum or receiving selective semistarvation an oral Ca supplement to obtain additional weight-matched intake-matched control groups. Diabetic had markedly increased food intake, so their net balance remained positive despite 13-fold increase urinary excretion disappearance active duodenal absorption. Decreased uptake correlated decreased...

It has been recently suggested that high glucose infusion rates during euglycemic hyperinsulinemia result in accumulation of free human skeletal muscle (J. Clin. Invest. 76: 357, 1985). To examine this possibility, we performed a euglycemic, hyperinsulinemic clamp together with biopsies from the quadriceps femoris on seven healthy men. Insulin was infused at successive 40 and 400 mU. m-2.min-1, resulting mean plasma insulin concentrations 69 +/- 3 1,285 115 (SE) microU/ml, respectively....

Adipocytes are the primary cells in body that store excess energy as triglycerides. To perform this specialized function, adipocytes rely on their mitochondria; however, role of adipocyte mitochondria regulation adipose tissue homeostasis and its impact metabolic is not understood. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) adipocytes. Mito-Ob mice obesity due to upregulation mitochondrial biogenesis Of note, female more visceral fat than male mice....

The majority of insulin-like growth factor I (IGF-I) circulates in blood bound to a family IGF-binding proteins (IGFBPs). Only small fraction IGF-I is unbound or free, and one the postulated roles IGFBPs regulation this free component, thereby increasing bioavailability. Whether plays physiological role glucose homeostasis, however, not clear. In study, we examined effects acute changes serum insulin on IGF-I, total IGFBP-1, IGFBP-3 11 healthy subjects. Glucose (0.3 g/kg) (0.05 U/kg) were...

Prenatal alcohol exposure (EtOH) results in insulin resistance rats of both sexes with increased expression hepatic gluconeogenic genes and glucose production. To investigate whether signaling is defective, we studied 3-mo-old female offspring dams that were given EtOH during pregnancy compared those from pair-fed control dams. We performed an intraperitoneal pyruvate tolerance test, determined the phosphorylation status phosphoinositide-dependent protein kinase-1 (PDK1), Akt, PKCzeta before...

Pancreatic beta-cell dysfunction is a prerequisite for the development of type 2 diabetes. Alcoholism diabetes risk factor and ethanol increases oxidative stress in beta-cells, whereas mitochondrial chaperone prohibitin (PHB) has antioxidant effects several cell types. In present study we investigated whether PHB expressed beta-cells protects these cells against deleterious ethanol, using INS-1E RINm5F lines. Endogenous was detected by western blot immunocytochemistry. Reactive oxygen...

Abstract Obesity increases the risk for nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. However, underlying mechanisms involved in disease process remain unclear. Recently, we have developed a transgenic obese mouse model (Mito-Ob) by prohibitin mediated mitochondrial remodeling adipocytes. The Mito-Ob mice develop obesity sex-neutral manner, but obesity-associated adipose inflammation metabolic dysregulation male sex-specific manner. Here report that with aging, spontaneously...

High-fat diet and intrauterine growth retardation may predispose to obesity, insulin resistance, type 2 diabetes. Because prenatal ethanol (ETOH) exposure causes retardation, we investigated its interactions with postnatal high-fat on glucose tolerance adipocyte-derived hormones in the rat offspring. High-fat-fed offspring had increased adiposity, serum leptin, muscle uncoupling protein-3, but decreased adiponectin mRNA, compared corresponding chow-fed groups. ETOH-exposed normal...