Hormonal regulation of skeletal muscle glycogen synthase through covalent phosphorylation.

Studies have been initiated to determine the hormonal regulation of glycogen synthase in rabbit skeletal muscle. It was found that glycogen synthase purified from control animals was quite highly phosphorylated (2.35 mol phosphate/mol synthase subunit) with 40% of the phosphate in the trypsin-sensitive or COOH-terminal domain, and 60% in the trypsin-insensitive or NH2-terminal domain. The phosphorylation state of synthase was elevated (3.9 mol/mol) by epinephrine injection and in the diabetic condition. With epinephrine, about 76% of the additional phosphate was incorporated in the trypsin-sensitive domain, which strongly supports the contention that this hormone acts through the cyclic AMP (cAMP)-dependent protein kinase. In the synthase purified from diabetic rabbits, 90% of the additional phosphate was in the trypsin-insensitive domain. Insulin treatment of the diabetics resulted in specific dephosphorylation of the trypsin-insensitive domain. These results indicate that in this system insulin is not acting by inhibition of the cAMP-dependent protein kinase.