Evidence that increased glucose cycling in islets of diabetic ob/ ob mice is a primary feature of the disease. Efendic, Akhtar Khan Suad. Department of Molecular Medicine. Karolinska Hospital, S-171 76 Stockholm, Sweden
APStracts 2:0106E, 1995.
Glucose cycling (GC) is increased in pancreatic islets from hyperglycemic 6-month old ob/ob mice. We determined whether normalization of glycemia alters islet GC and insulin release in response to glucose as well as oxidation and utilization of the glucose. Mice were treated with phlorizin in DMSO for 10 days which resulted in normalization of blood glucose concentrations. Controls received DMS0. The mice were fasted overnight, killed and their islets isolated for measurements of insulin release at 5.5mM and 16.7mM glucose and at 16.7mM glucose plus 10mM arginine. GC was measured by the incorporation of 3H from 3H20 into carbon-2 of glucose, glucose oxidation by the yield of 14C02 from [U-14C]glucose and glucose utilization by the yield of 3H20 from [5-3H]glucose. Phlorizin treatment did not alter the response of insulin to glucose and to glucose plus arginine. GC was 30% in the control and phlorizin treated animals. Glucose oxidation and utilization were also the same in both groups. In fed, 10-12 month old, mice exhibiting a broad range of blood glucose levels, there was no correlation between GC and either insulin release or glucose concentrations. Thus, the islets of ob/ob mice exhibit an increased rate of GC irrespective of glycemia. This indicates that the increased rate of GC is an important characteristic of the diabetic syndrome in these animals and not simply secondary to hyperglycemia.

Received 24 March 1995; accepted in final form 10 May 1995.
APS Manuscript Number E138-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.