Selective stimulation of glucagon secretion by beta 2-adrenoceptors in isolated islets of Langerhans of the rat.
1. In rat isolated islets of Langerhans the selective beta 2-adrenoceptor agonist, clenbuterol (1 to 20 microM), significantly increased the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) within 2 min of incubation. 2. The cyclic AMP response to clenbuterol was inhibited in the presence of the selective beta 2 adrenoceptor antagonist, ICI 118551 (0.1 or 10 microM) but remained unchanged when the beta 1-antagonist, atenolol (0.1 microM) was administered. 3. Despite causing an elevation in cyclic AMP, clenbuterol (up to 20 microM) failed to influence insulin secretion at any glucose concentration tested, even in the presence of a phosphodiesterase inhibitor. 4. By contrast, clenbuterol elicited a dose-dependent rise in the rate of glucagon secretion; the maximal agonist-induced increase in secretion was two fold, a response equivalent to that observed with 20 mM L-arginine. 5. ICI 118551 significantly inhibited the rise in glucagon secretion induced by clenbuterol (up to 20 microM). 6. The results indicate that the rat islet A cell population is equipped with functional beta 2-adrenoceptors which influence glucagon secretion via the second messenger cyclic AMP, but that the B cells are deficient in functional beta-receptors.
Lacey
R J
RJ
Department of Biological Sciences, University of Keele, Staffordshire.
Berrow
N S
NS
Scarpello
J H
JH
Morgan
N G
NG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D007328:Insulin; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C026777:ICI 118551; D001262:Atenolol; D005934:Glucagon; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; D002976:Clenbuterol