Gene expression of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects.

The gene of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase gives rise to several splice variants. We hypothesized that the expression of p85alpha splice variants may be altered in skeletal muscle from subjects with type 2 diabetes mellitus. Skeletal muscle biopsies were obtained from nine type 2 diabetic and eight healthy men, matched for age, body mass index (BMI) and physical fitness.

Isoform-specific regulation of 5' AMP-activated protein kinase in skeletal muscle from obese Zucker (fa/fa) rats in response to contraction.

Glucose transport can be activated in skeletal muscle in response to insulin via activation of phosphoinositide (PI) 3-kinase and in response to contractions or hypoxia, presumably via activation of 5' AMP-activated protein kinase (AMPK). We determined the effects of insulin and muscle contraction/hypoxia on PI 3-kinase, AMPK, and glucose transport activity in epitrochlearis skeletal muscle from insulin-resistant Zucker (fa/ fa) rats. Insulin-stimulated glucose transport in isolated skeletal muscle was reduced 47% in obese versus lean rats, with a parallel 42% reduction in tyrosine-associated PI 3-kinase activity.

Analysis of paradoxical observations on the association between leptin and insulin resistance.

Obesity is commonly associated with the development of insulin resistance and diabetes in humans and rodents. Insulin resistance and diabetes are observed in lipoatrophic individuals or rodent models of lipoatrophy. Here we focus on the role of leptin, the product of the obesity (ob) gene, in the development of insulin resistance and diabetes associated with obesity and lipoatrophy.

Invited review: Exercise training-induced changes in insulin signaling in skeletal muscle.

This review will provide insight on the current understanding of the intracellular signaling mechanisms by which exercise training increases glucose metabolism and gene expression in skeletal muscle. Participation in regular exercise programs can have important clinical implications, leading to improved health in insulin-resistant persons. Evidence is emerging that insulin signal transduction at the level of insulin receptor substrates 1 and 2, as well as phosphatidylinositol 3-kinase, is enhanced in skeletal muscle after exercise training.

From receptor to effector: insulin signal transduction in skeletal muscle from type II diabetic patients.

Insulin resistance is a characteristic feature of type II diabetes mellitus and obesity. Although defects in glucose homeostasis have been recognized for decades, the molecular mechanisms accounting for impaired whole body glucose uptake are still not fully understood. Skeletal muscle constitutes the largest insulin-sensitive organ in humans; thus, insulin resistance in this tissue will have a major impact on whole body glucose homeostasis.