Gene expression of the p85α regulatory subunit of phosphatidylinositol 3-kinase in skeletal muscle from type 2 diabetic subjects

Abstract.

The gene of the p85α regulatory subunit of phosphatidylinositol (PI) 3-kinase gives rise to several splice variants. We hypothesized that the expression of p85α 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. PI 3-kinase activity in skeletal muscle following in vitro insulin stimulation was reduced in subjects with type 2 diabetes. p85α mRNA was elevated fourfold in type 2 diabetic as compared to healthy control subjects (P<0.05). p85α mRNA abundance was positively correlated with plasma insulin concentration (P<0.01) and serum glucose concentration (P<0.01). Despite this, protein levels of p85α, p55α, and the novel human p50α were not altered in type 2 diabetic subjects. Thus, although gene expression of full-length p85α is increased in skeletal muscle from type 2 diabetics, this is not reflected by increased protein levels. Therefore, defects in PI 3-kinase activity are likely due to impaired activation of the enzyme rather than changes in protein expression of the isoforms of the regulatory subunit.