Presence, induction and possible role of glucose 6-phosphatase in mammalian pancreatic islets

1. Pancreatic islets from several mammalian species were investigated for hydrolytic activity towards glucose 6-phosphate. Both the total phosphatase activity towards this substrate and the proportion cleaving glucose 6-phosphate in preference to β-glycerophosphate varied widely between species. In pancreatic-islet homogenates prepared from mice and guinea pigs there was a higher rate of liberation of P_i at pH6·7 from glucose 6-phosphate than from β-glycerophosphate. In these two species cortisone treatment enhanced the enzyme activity towards glucose 6-phosphate but not that towards β-glycerophosphate. Simultaneous injections of ethionine or puromycin blocked this stimulating effect of cortisone. 2. With whole homogenates of mouse pancreatic islets, inverse plots of the relationship between glucose 6-phosphate concentration and enzyme activity suggested the simultaneous action of two enzymes with different K_m values. After fractionation of islets from obese–hyperglycaemic mice by differential centrifugation, one of these enzymes could be shown to be localized in the microsome fraction. It had K_m for glucose 6-phosphate about 0·5mm and optimum pH6·7. It split glucose 6-phosphate in preference to β-glycerophosphate, glucose 1-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate. Incubation of the microsomes at pH5·0 and 37° for 15min. decreased the enzyme activity by about 80%. Glucose was a potent inhibitor, the type of inhibition being neither strictly competitive nor non-competitive. It is suggested that the results indicate the presence of glucose 6-phosphatase in mammalian endocrine pancreas, and that this enzyme may play a role in the metabolic regulation of release of insulin.     

Plasma Insulin during Remission in Juvenile Diabetes Mellitus

Three juvenile diabetics in partial remission were studied before and after the recurrence of overt diabetes. The remissions were partial because glucose tolerance never returned to normal. However, it improved sufficiently to cause the discontinuance of insulin therapy for at least four months.The insulin output in response to double glucose tolerance tests was increased during remission. The degree of remission seemed to be related to the magnitude of the insulin response to glucose. In two of the patients the increase was low and the response very slight. The third patient, however, had a delayed hyper-response and his carbohydrate tolerance during the remission was much more improved than those of the other patients.