Impaired insulin secretion and excessive hepatic glucose production
are both early events in the diabetic gk rat.
Picarel-Blanchot, Fran[cedilla]coise, C[acute]ecile Berthelier,
Danielle Bailbe, and Bernard Portha.
Lab. Physiopathologie Nutrition, CNRS URA 0307, Universit[acute]e
Paris 7 / D. Diderot, 2 place Jussieu, 75251 Paris Cedex 05,
France
APStracts 3:0120E, 1996.
Adult GK rats exhibit a spontaneous non-insulin dependent diabetes
characterized by impaired glucose-induced insulin secretion,
decreased [beta] cell mass, hepatic glucose overproduction and
moderate insulin resistance in muscles and adipose tissues. To
elucidate the pathogenesis of hyperglycemia in this animal model, we
have studied insulin secretion and insulin action in 4 wk-old GK
pups, just before weaning. In the post-absorptive state, their basal
plasma glucose was elevated (p < 0.001) and their tolerance to
i.v. glucose was impaired. Their kinetic of insulin release in
response to glucose was impaired, with a low acute phase of insulin
release in vivo as well as in vitro (perfused pancreas). Basal
glucose production was increased in the GK pups by 40% (p <
0.05). During euglycemic clamp performed at submaximal
hyperinsulinemia, suppression of liver glucose production was less
effective (p < 0.01) in the GK rats, while their overall glucose
utilization was similar to that of the controls. This was correlated
with a normal insulin-stimulated glucose utilization by
epitrochlearis, soleus and extensor digitorus longus muscles,
diaphragm and white adipose tissues. These data give body to the
primacy of the [beta] cells defects in the etiology of NIDDM in the
GK rat. They also highlight a possible primary role of the liver
defect. Peripheral insulin resistance does not contribute to the
development of postnatal glucose intolerance in this diabetes model.
Received 22 January 1996; accepted in final form 6 June 1996.
APS Manuscript Number E37-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96