Modulation of gliquidone action by forskolin in the pancreas of normal and GK rats.
This study aims to investigate whether agents that stimulate adenosine 3',5'-cyclic monophosphate (cAMP) 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 microM) on 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 microM). In normal rats, the diterpene exerted relatively little effect on 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, while 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 light of a dual metabolic and energy-independent response of islet cells to the forskolin-induced generation of cAMP. They document the optimalization by endogenous cAMP of the B cell secretory response to gliquidone in non-insulin-dependent diabetes.
Leclercq-Meyer
V
V
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Malaisse
W J
WJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012016:Reference Values; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D005576:Colforsin; D005934:Glucagon; C010969:gliquidone; D005947:Glucose