Diabetes in the Toronto-KK hybrid mouse abnormalities in liver and pancreatic islets of Langerhans

Abstract

The activities of six hepatic enzymes were assayed in six-month old Toronto-KK and C57BL/6J mice. Activities of hepatic gluconeogenic enzymes (phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fructose-1,6-diphosphatase) were significantly elevated in Toronto-KK mice while activities of glycolytic enzymes (glucokinase, hexokinase, pyruvate kinase) remained normal. Isolated islets of Langerhans obtained from Toronto-KK mice demonstrated significantly elevated levels of insulin secretion and of insulin and RNA biosynthesis in response to glucose stimulation. Islets of Toronto-KK mice were markedly hyperplastic and showed pronounced B-cell degranulation after stimulation with glucose. The data suggest that hyperglycemia appears to result, in part, from excessive gluconeogenesis. Hyperinsulinemia appears to result from excessive insulin synthesis and release from the pancreatic islets in response to glucose stimulation. © 1974 Springer-Verlag.