In accordance with peripheral (muscle) insulin resistance developing first, and therefore having a larger deficit (as measured by the hyperinsulinemic-euglycemic clamp), insulin-stimulated activation of skeletal muscle atypical protein kinase Cs-(ζ/λ/ι), insulin receptor substrate (IRS)-1, phosphatidylinositol (PI) 3-kinase, PKB, and glycogen synthase have all been shown to be decreased in dysmetabolic monkeys [8, 41, 42]. This evidence concerns the gene IRS1 and Insulin resistance.