Effect of long-term caloric restriction on GLUT4, phosphatidylinositol-3 kinase p85 subunit, and insulin receptor substrate-1 protein levels in rhesus monkey skeletal muscle

Caloric restriction (CR), a reduction in calorie intake without malnutrition, improves insulin sensitivity in various species, including mice, rats, rhesus and cynomolgus monkeys, and humans. Skeletal muscle is quantitatively the most important tissue for blood glucose clearance. Therefore, we assessed the effect of 6 years of CR (30% reduction in calorie intake) in male rhesus monkeys (14-20 years old) on muscle expression of several proteins involved in insulin action. Whole body insulin sensitivity (assessed by Modified Minimal Model) was significantly increased in CR relative to Control monkeys. CR did not alter the expression of GLUT4 glucose transporter or phosphatidylinositol-3 kinase p85 subunit (PI3K). Insulin receptor substrate-1(IRS-1) abundance tended to be greater for CR compared to Control monkeys (p = .051), but correlational analysis revealed no association between IRS-1 and insulin sensitivity (r2 = .075, p = .271). These findings indicate that the CR-induced increase in insulin sensitivity in rhesus monkeys is unrelated to alterations in GLUT4, P13K, and IRS-1 abundance.