IN-VIVO D-CHIROINOSITOL ACTIVATES SKELETAL-MUSCLE GLYCOGEN-SYNTHASE AND INACTIVATES GLYCOGEN-PHOSPHORYLASE IN RHESUS-MONKEYS

Chiroinositol, a component of an inositol phosphoglycan, has been found to be reduced in the urine of humans and monkeys with non-insulin-dependent diabetes mellitus. To determine whether in vivo repletion of this inositol could improve the action of insulin on skeletal muscle glycogen synthase and glycogen phosphorylase, D-chiroinositol was administered intravenously to sir monkeys during a euglycemic hyperinsulinemic clamp. Enzyme activities were determined in vastus lateralis which was freeze-clamped in situ at three time periods: immediately prior to initiation of the clamp, after steady-state glucose and insulin concentrations had been reached and the glucose disposal rate determined, and 30 min after the administration of D-chiroinositol which was superimposed on the steady-stare clamp condition. D-chiroinositol increased the activity (independent and fractional velocity) of glycogen synthase (P < 0.05) and decreased the activity (independent and activity ratio) of phosphorylase (P < 0.05) compared with the samples during the clamp immediately prior to D-chiroinositol administration. Total activities of glycogen synthase and glycogen phosphorylase were not different between any of the conditions studied. We conclude that intravenous administration of D-chiroinositol enhances intracellular insulin action on muscle glycogen synthase and glycogen phosphorylase in rhesus monkeys.