Differential regulation of glycogen synthase by insulin and glucose in vivo in skeletal muscles of the rat

B-phosphate (G-6-P)-independent glycogen synthase (GSa) and glycogen synthase (GS) total activities were measured in muscles from 24-h-starved rats. Intravenous glucose tolerance tests (0.5 g/kg body wt) were used to produce physiological, transient increases in insulin and glucose concentrations. GS activation occurred at approximate to 10 min after glucose administration with peak activation at approximate to 15 min. GS activation was reversed approximate to 15 min after insulin and glucose concentrations had returned to basal. No differences existed between fast-and slow-twitch muscles. Hyperinsulinemia (approximate to 160 mU/ml) in the absence of hyperglycemia elicited 1.5-fold activation of GS (P < 0.001) in two of three fast-twitch muscles but did not activate GS in slow-twitch muscles. Glucose infusion (glycemia approximate to 8 mM; insulin approximate to 40 mU/ml) significantly (P < 0.01) increased the percentage of total GS in the GSa form in four of the five muscles. Hyperglycemia with modest hyperinsulinemia evoked greater enhancement of GSa activity in fast-twitch muscle than insulin alone at a higher concentration (P < 0.01). In summary, hyperinsulinemia without hyperglycemia does not result in maximal activation of GS in fast-twitch muscle, and a rise in glycemia is obligatory for GS activation by insulin in slow-twitch muscle. The data support an important role for glycemia in modulating the response of skeletal muscle GS to insulin and provide further evidence of heterogeneity among skeletal muscle types.