The glucose effect: Carbohydrate repression of enzyme induction, RNA synthesis, and glucocorticoid activity — A role for cyclic AMP and cyclic GMP

Abstract

Feeding a variety of carbohydrates (but not all carbohydrates) to mammals results in blocking the induction of many enzymes involved in amino acid metabolism as well as stimulation of some enzymes which participate in glucose utilization. In addition, glucocorticoid activity, both catabolic and anabolic, is inhibited; alterations in nuclear morphology become apparent, and m-RNA synthesis is greatly depressed. Evidence clearly opposes the mediation of the glucose effect by insulin. In bacteria, similar events following glucose feeding are caused by a 90% drop in cyclic AMP levels. But only a relatively small (20%) reduction occurs in mammals; however, the concentration of the antagonist of cyclic AMP — cyclic GMP — is considerably increased, thereby producing a functional decrease in the activity of cyclic AMP. Some, not all, of the glucose effect can be reproduced by the administration of bromo-cyclic-GMP, indicating that part of the glucose effect is mediated by elevation of the guanosine cyclic nucleotide.