Decreased glucose-induced camp and insulin release in islets of
diabetic rats; reversal by ibmx, glucagon or gip.
Dachicourt, N., P. Serradas, M. H. Giroix, M. N. Gangnerau, and B.
Portha.
Laboratoire de Physiopathologie de la Nutrition - CNRS URA 307,
Universit[acute]e Paris 7 - Denis Diderot, Place Jussieu, Tour 33-43,
1er [acute]etage - 75 251 Paris cedex 05, France
APStracts 3:0121E, 1996.
The first aim of the study was to investigate the possibility that a
defect on the islet cAMP production could be involved in the failure
of the glucose-induced insulin secretion in the neonatal
streptozotocin diabetic rats. Exposure to glucose concentration that
induced a rise of the cAMP content in the control islets did not
elicited any significant increase in cAMP in diabetic islets.
Forskolin, isobutylmethylxanthine, glucagon or pertussis-toxin,
amplified the cAMP accumulation and the insulin release, to the same
extent in both types of islets. Somatostatin, PG-E2, UK-14304 or
galanin inhibited cAMP accumulation and insulin release to the same
extent in both types of islets. Our second purpose was to investigate
whether the use of activators of adenylate cyclase could restore the
[beta]-cell competence to glucose in diabetic rats. The addition of
IBMX, glucagon or GIP to perifused islets of diabetic rats amplified
their insulin response to glucose and a clear biphasic pattern of the
release was regained. In conclusion, while there is no major
alteration of the functionality of the adenylate cyclase in the
[beta]-cells of the diabetic rats, we have identified a defective
glucose-induced cAMP generation, which could be explained by a block
in the step(s) linking glucose metabolism and activation of adenylate
cyclase.
Received 13 November 1995; accepted in final form 5 June 1996.
APS Manuscript Number E538-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96