title: Effects of alpha 2- and beta-adrenergic agonism on glucagon secretion from perfused pancreata of normal and streptozocin-induced diabetic rats.
abstract: Insulin secretion is known to be inhibited by alpha 2-adrenergic agonism and stimulated by beta-adrenergic agonism in both experimental animals and humans. In contrast, adrenergic regulation of glucagon secretion remains controversial. This study was designed to determine the effects of alpha 2- and beta-adrenergic agonism on islet alpha cells, using isolated perfused pancreata of normal and streptozocin-induced diabetic (STZ-D) rats. The alpha 2-adrenoceptor agonist clonidine at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (1,286 +/- 90 v 417 +/- 53 ng/L, P < .01) and STZ-D rats (551 +/- 86 v 130 +/- 19 ng/L, P < .01). Also, the beta-adrenoceptor agonist isoproterenol at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (751 +/- 130 v 347 +/- 41 ng/L, P < .05) and STZ-D rats (182 +/- 22 v 92 +/- 20 ng/L, P < .01). Furthermore, these alpha 2- and beta-agonistic effects were almost completely inhibited in the presence of the alpha 2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol at a concentration of 10(-6) mol/L, respectively. Insulin secretion was markedly reduced in STZ-D rats. These results suggest that even in a severely diabetic state, not only beta- but also also alpha 2-adrenergic agonism stimulates glucagon secretion from rat pancreatic alpha cells.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hirose
authors.forename: H
authors.initials: H
authors.lastname: Maruyama
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Kido
authors.forename: K
authors.initials: K
authors.lastname: Koyama
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007328:Insulin; D015016:Yohimbine; D013311:Streptozocin; D005934:Glucagon; D011433:Propranolol; D005947:Glucose; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine