The purpose of this study was to examine the effects of 6 month trial of AEX and WL on signaling pathways (Akt, GSK-3β, 70S6K, ERK 1/2, JNK, P38K), and the terminal inhibitory action on IRS-1 tyrosine phosphorylation, IGF-1R, and the IR in the basal state and during hyperinsulinemia in middle-aged and older overweight and obese individuals, and whether the changes in expression and signal transduction are associated with changes in peripheral/whole body insulin sensitivity by a hyperinsulinemic-euglycemic clamp. This evidence concerns the gene IRS1 and hyperinsulinism.