Prevention of diabetes does not completely prevent insulin
secretory defects in the zucker diabetic fatty rat.
Sturis, Jeppe, William L. Pugh, Jiping Tang, and Kenneth S. Polonsky.
The Department of Medicine, The University of Chicago, Pritzker
School of Medicine, Chicago, IL 60637
APStracts 2:0116E, 1995.
The rapid insulin secretory pulses which occur in the perfused rat
pancreas can be entrained by an oscillatory glucose concentration in
pancreata from nondiabetic rats, but not from diabetic Zucker
Diabetic Fatty (ZDF) rats. To investigate whether this defect is
present in prediabetic ZDF rats and whether treatment with either
pioglitazone or acarbose can prevent or reverse this defect, 39 ZDF
and five lean ZDF Control rats were studied. The ZDFs were divided
into six groups depending on age, form of therapy used, and the time
at which pioglitazone was started in relation to the onset of
diabetes. The pancreas was isolated and perfused using a sine-wave
shaped glucose concentration (mean 7 mM, period 10 min, amplitude
10%). The results, assessed by spectral analysis, revealed that in
prediabetic animals and in controls, entrainment of pulsatile insulin
secretion was normal. Initiation of pioglitazone therapy in ZDFs at
the time of weaning or before diabetes onset prevented hyperglycemia.
However, entrainment was only partially retained. Thus, in these two
groups, the spectral power at 10 min was greater than in untreated
animals, but lower than in prediabetic and control animals. Treatment
with acarbose before or with pioglitazone after diabetes onset
improved, but did not normalize glucose levels, and did not improve
entrainment. The results demonstrate the presence of insulin
secretory defects in 13-week old ZDF rats in whom hyperglycemia was
prevented.
Received 28 February 1995; accepted in final form 15 May 1995.
APS Manuscript Number E93-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.