B cell adrenoceptors and sulphonylurea-induced insulin release in mouse islets.
Interactions of tolbutamide and glibenclamide with B cell adrenoceptors have been reported. This study evaluated the possible role of such interactions in the stimulation of insulin release. Mouse islets were incubated in the presence of 10 mmol/l glucose alone or with tolbutamide (10 mumol/l) or glibenclamide (0.02 mumol/l). At 0.01-10 mumol/l, blockers of alpha 2-adrenoceptors (yohimbine, idazoxan) or alpha 1-adrenoceptors (prazosin) had practically no effect on glucose-induced insulin release and did not affect its potentiation by sulphonylureas, except for a slight increase by 10 mumol/l prazosin and idazoxan. Nonspecific alpha-blockers (phentolamine, dihydroergotamine) increased control release at 10 mumol/l, but only the latter amplified the response to tolbutamide. Blockers of beta-adrenoceptors were tested at 0.1-100 mumol/l: propranolol (beta 1, beta 2), metoprolol (beta 1) and compound ICI 118-551 (beta 2). They increased glucose-induced insulin release at 100 mumol/l but variably altered the effect of sulphonylureas. Blockers of adrenoceptors have, thus, no effect on insulin release in vitro at therapeutic concentrations. At high concentrations, they non-specifically affect the action of sulphonylureas. We conclude that an interaction with B cell adrenoceptors is not involved in the insulinotropic action of sulphonylureas.
Garrino
M G
MG
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Henquin
J C
JC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D007328:Insulin; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D014044:Tolbutamide; D011433:Propranolol; D008790:Metoprolol; D005905:Glyburide