REGULATION OF EXOGENOUS AND ENDOGENOUS GLUCOSE-METABOLISM BY INSULIN AND ACETOACETATE IN THE ISOLATED WORKING RAT-HEART - A 3 TRACER STUDY OF GLYCOLYSIS, GLYCOGEN-METABOLISM, AND GLUCOSE-OXIDATION

Myocardial glucose use is regulated by competing substrates and hormon al influences, However, the interactions of these effecters on the met abolism of exogenous glucose and glucose derived from endogenous glyco gen are not completely understood, In order to determine changes in ex ogenous glucose uptake, glucose oxidation, and glycogen enrichment, he arts were perfused with glucose (5 mM) either alone, or glucose plus i nsulin (40 mu U/ml), glucose plus acetoacetate (5 mM), or glucose plus insulin and acetoacetate, using a three tracer (H-3, C-14, and C-13) technique. Insulin-stimulated glucose uptake and lactate production in the absence of acetoacetate, while acetoacetate inhibited the uptake of glucose and the oxidation of both exogenous glucose and endogenous carbohydrate. Depending on the metabolic conditions, the contribution of glycogen to carbohydrate metabolism varied from 20-60%. The additio n of acetoacetate or insulin increased the incorporation of exogenous glucose into glycogen twofold, and the combination of the two had addi tive effects on the incorporation of glucose into glycogen. In contras t, the glycogen content was similar for the three groups, The increase d incorporation of glucose in glycogen without a significant change in the glycogen content in hearts perfused with glucose, acetoacetate, a nd insulin suggests increased glycogen turnover, We conclude that insu lin and acetoacetate regulate the incorporation of glucose into glycog en as well as the relative contributions of exogenous glucose and endo genous carbohydrate to myocardial energy metabolism by different mecha nisms.