Mechanism of puromycin activation of tadpole liver glycogen synthetase

Abstract

Tadpole liver glycogen synthetase (EC 2.4.1.11), which is completely glucose 6-phosphate dependent, is activated by insulin. Puromycin mimics the hormone and activates the enzyme to a similar degree. The antibiotic initiates a series of events which appears to result in the release of insulin. Inhibition of cyclic phosphodiesterase by puromycin raises hepatic cyclic AMP to a level which stimulates phosphorylase b kinase. The increased glycogenolysis, depletion of liver glycogen and hyperglycemia which result would lead to the release of insulin. By using alloxan-treated and pancreatectomized tadpoles we have shown that the puromycin activation of glycogen synthetase is contigent on functional β-cells in the pancrease to produce insulin.