Modulation of gliquidone action by forskolin in the pancreas of
normal and gk rats.
Leclercq-Meyer, Viviane, and Willy J. Malaisse.
Laboratory of Experimental Medicine, Brussels Free University, B
-1070 Brussels, Belgium
APStracts 4:0073E, 1997.
This study aims at investigating whether agents which stimulate cyclic
AMP formation could be used to increase insulin release evoked by
hypoglycemic sulfonylureas in non-insulin-dependent diabetes
mellitus. For this purpose, the effect of gliquidone (1.0 [mu]M) upon
insulin and glucagon release was examined in the perfused pancreas of
either normal or Goto-Kakizaki (GK) rats at a low concentration of D
-glucose (2.8 mM) and in the absence or presence of forskolin (1.3
[mu]M). In normal rats, the diterpene exerted relatively little
effect upon basal insulin release, but markedly augmented the
insulinotropic action of gliquidone. In GK rats, forskolin
dramatically augmented both basal and gliquidone-stimulated insulin
output. In mirror image of its effect on insulin release, forskolin
augmented basal glucagon output and failed to increase the secretory
response of the A-cell to gliquidone, at least in normal rats. On the
contrary, in GK rats, forskolin, whilst slightly enhancing basal
glucagon output, unmasked the glucagonotropic potential of
gliquidone, that was otherwise not detected in the diabetic animals.
These findings are interpreted in the light of a dual -metabolic or
energy-independent- response of islet cells to the forskolin-induced
generation of cyclic AMP. They document the optimalization by
endogenous cyclic AMP of the B-cell secretory response to gliquidone
in non-insulin-dependent diabetes.
Received 20 September 1996; accepted in final form 20 March 1997.
APS Manuscript Number E476-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 3 April 1997