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  • Title: Insulin secretagogues with an imidazoline structure inhibit arginine-induced secretion from isolated glucagon secretion from isolated rat islets of Langerhans.
    Author: Mourtada M, Smith SA, Morgan NG.
    Journal: Biochem Biophys Res Commun; 1997 Jul 09; 236(1):162-6. PubMed ID: 9223445.
    Abstract:
    It is well documented that imidazoline compounds such as efaroxan and phentolamine act as potent insulin secretagogues both in vivo and in vitro, an effect which is mediated principally by blockade of ATP-sensitive potassium channels in the pancreatic B-cell. However, little is known about the effects of these drugs on the secretion of other pancreatic hormones and, in the present work, we have investigated the effects of selective imidazoline compounds on glucagon release from isolated rat islets of Langerhans. None of several imidazoline compounds tested (efaroxan, phentolamine, idazoxan, antazoline) affected glucagon secretion from islets incubated with 4 mM glucose. However, when the rate of glucagon release was stimulated by L-arginine (20 mM) efaroxan caused a rapid, sustained and dose-dependent inhibition of the secretory response (EC50 approximately 30 microM). This effect was seen under both static incubation and islet perifusion conditions. Antazoline and phentolamine also inhibited arginine-induced glucagon secretion, whereas idazoxan (an imidazoline which does not affect insulin secretion) failed to alter glucagon release. The inhibitory effects of imidazolines on glucagon release were not secondary to changes in insulin secretion. Taken together, the results indicate that pancreatic A-cells express functional imidazoline receptors which can regulate the secretory activity of the cells.
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