Calorie restriction increases insulin-stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 in rat skeletal muscle

A moderate reduction in calorie intake (calorie restriction, CR) improves i nsulin-stimulated glucose transport in skeletal muscle. Therefore, we studi ed muscle insulin signalling in ad libitum (AL) and CR (similar to 60% AL i ntake for 20 days) fed rats, which received a control injection (sterile wa ter) or an insulin injection (30 U kg(-1) body weight). in control (not ins ulin-treated) rats, there was no detectable tyrosine phosphorylation of ins ulin receptor (IR), regardless of diet; no diet effect on tyrosine phosphor ylation of insulin receptor substrate-1 (IRS1) or IRS1-associated phosphati dylinositol 3-kinase (PI3K) protein and 21% higher IRS1-associated P13K act ivity in AL vs. CR. In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated P13K protein and IRS1-associated P13K activity were unaffected by diet. Calorie restriction amplifies early insulin signal ling steps without changing IRS1-associated PI3K, suggesting enhanced gluco se transport is mediated by altering: IRS1-PI3K localization, P13K associat ed with proteins other than IRS1 or post-PI3K events.