Abnormalities in hepatic enzyme activities during development of diabetes in db mice.

Abstract

Seven hepatic enzymes were assayedin vitro in diabetic and control C57BL/Ks mice at 1, 2, and 41/2 month. An elevation in phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was observed before the onset of hyperglycemia in db mice at the age of 1 month. At two months, these mice had hyperglycemia, hyperinsulinemia and high levels of phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate kinase and 6-phosphogluconate dehydrogenase. The 4 1/2 month old db mice had normal plasma insulin, severe hyperglycemia, exorbitant amount of hepatic gluconeogenic enzymes and reduced quantity of glycolytic and pentose-phosphate shunt enzymes. The disturbance in enzyme activities and blood sugar was partially controlled by placing the animals on a limited diet beginning at the age of 1 month.In vivo studies indicated that hyperglycemia resulted, at least in part, from an accelerated rate of gluconeogenesis. The development of diabetes in these mice is discussed with reference to these findings.