The relationship between insulin and apparent glucocorticoid-promoted activation of hepatic glycogen synthetase

Abstract

The early (2 h) cortisol-induced activation of hepatic glycogen synthetase in adrenalectomized rats was lost during the course of development of the diabetic state with alloxan. Significant increases in glycogen synthetase D phosphatase activity accompanied the increases in glycogen synthetase I activity and hepatic glycogen deposition was observed in nondiabetic rats 2 h after cortisol administration. These enzyme activities, however, were unchanged over the 6-h period studied in diabetic rats given steroid in which delayed and considerably smaller increases in glycogen deposition were found at 4 and 6 h but not at earlier time periods. The diminished levels of phosphatase activity in alloxan diabetic rats were significantly increased within 10 min after insulin administration and paralleled increases in the levels of glycogen synthetase in the I form. Increases in glycogen synthetase I activity were observed within 2 to 4 min in adrenalectomized alloxan diabetic rats given insulin but no change in the concentration of adenosine 3′,5′-monophosphate (cyclic AMP) was detected until 6 to min when no more than a 17% decrease was recorded. It was concluded that the early glucocorticoid induced effects on the hepatic glycogen synthetase system seem to be mediated by a release of insulin promoted directly or indirectly as a result of steroid action. The increases in glycogen deposition at later times (4–6 h) after cortisol are markedly inhibited in diabetic animals and are not associated with significant increases in the activities of glycogen synthetase D phosphatase or glycogen synthetase. The rapid activation of glycogen synthetase following insulin administration in adrenalectomized diabetic rats appears to be mediated at least in part by a rapid restoration and/or activation of glycogen synthetase D phosphatese activity that may not be preceded by a lowering of hepatic cyclic AMP concentration.