Prevention of hyperglycemia in the zucker diabetic fatty rat by
treatment with metformin or troglitazone.
Sreenan, Seamus, Jeppe Sturis, William Pugh, Charles F. Burant, and
Kenneth S. Polonsky,.
Department of Medicine The University of Chicago and Pritzker
School of Medicine, Chicago, Illinois, 60637
APStracts 3:0129E, 1996.
To determine if metformin or troglitazone can delay the onset of
diabetes in the Zucker diabetic fatty (ZDF) rat, lean control, fatty
and ZDF rats received metformin, troglitazone or no treatment from
age 6 to 12 weeks. Glucose, insulin, triglyceride (TG) and free fatty
acid (FFA) levels and glucose stimulated insulin secretion by the
perfused pancreas were measured. Metformin-treated rats gained
significantly less weight. Both drugs prevented hyperglycemia by 12
weeks in diabetic rats and significantly reduced TG and FFA. Insulin
secretion at low glucose was elevated in untreated fatty and diabetic
animals and the increment in diabetic animals produced by glucose
perfusion was attenuated compared to lean and fatty rats. Both drugs
reduced basal insulin secretion in fatty and diabetic rats and
improved glucose responsiveness in diabetic rats. Metformin and
troglitazone delay onset of diabetes in the ZDF rat. The
significantly improved insulin secretory response of the pancreas
undoubtedly contributes to the improved glucose tolerance.
Received 23 October 1995; accepted in final form 12 June 1996.
APS Manuscript Number E509-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996