Insulin increases liver protein phosphatase-1 and protein phosphatase-2C activities in lean, young adult rhesus monkeys

Liver glycogen synthase activity is increased, and glycogen phosphorylase a ctivity and glucose 6-phosphate content reduced by in vivo insulin during a euglycemic hyperinsulinemic clamp in lean young adult rhesus monkeys. To e xamine the mechanism of dephosphorylation of liver glycogen synthase and gl ycogen phosphorylase, the enzyme activities of protein phosphatase-1, prote in phosphatase-2C, cAMP-dependent protein kinase, glycogen synthase kinase- 3, protein kinase C and protein tyrosine kinase were determined before and after three hours of in vivo insulin in these same monkeys. The bioactivity of an inositol phosphoglycan insulin mediator (pH 2.0) and cAMP concentrat ions were also measured in the liver before and after insulin administratio n. insulin caused significant increases in protein phosphatase-1 (p=0.005) and in protein phosphatase-2C activities (p = 0.001). Insulin-stimulated mi nus basal bioactivity of the pH 2.0 insulin mediator was strongly inversely related to the insulin-stimulated minus basal glucose 6-phosphate content (r = - 0.93, p<0.0001). These findings suggest that protein phosphatase-1 a nd protein phosphatase-2C may be involved in the mechanism of in vivo insul in activation of liver glycogen synthase and inactivation of liver glycogen phosphorylase.