Studies on Experimental Diabetes

Experimental diabetes has been characterized as a metabolic state involving both overproduction and underutilization of glucose. Although these changes have been recognized for many years, the specific biochemical alterations resulting in increased hepatic glucose production have not been adequately described. The adrenal cortical steroids are known, however, to have an important role in the regulation of this process (1). Previous studies from this laboratory have demonstrated that in alloxan diabetes there is an increase in the incorporation of Cl4 from labeled pyruvate and alanine into blood glucose (2). It would appear from our present knowledge of intermediary metabolism that the incorporation of labeled carbon atoms from 3 carbon glucogenic intermediates such as lactate, pyruvate, propionate, or alanine into hexose by hepatic tissue would require COz fixation (3-6). Furthermore, under conditions where increased hepatic glucose production would be expected, e.g. prior treatment with cortisone, incorporation of Cl4 from both pyruvate-2-C14 and C?Q into blood glucose is increased to a comparable extent (7). The present studies report observations on CY402 fisation in viva and in vitro and the influence of insulin insufficiency induced by alloxan and anti-insulin serum on this process.