Effects of adrenergic and cholinergic stimulation on islet monoamine oxidase activity and insulin secretion in the mouse.
It has been shown that the pancreatic beta-cell monoamines are located in the secretory granules, and that they have an inhibitory influence on insulin secretion. Monoamines are inactivated by the enzyme, monoamine oxidase. We now studied in vivo the relation between adrenergic and cholinergic stimulation, insulin secretion and islet monoamine oxidase activity in the mouse. Monoamine oxidase was assayed with three different substrates, serotonin, dopamine and beta-phenylethylamine. The alpha 2-adrenoceptor agonist, clonidine, induced a moderate inhibition (12-18%) of islet monoamine oxidase activity, accompanied by reduced plasma insulin and elevated plasma glucose levels. The alpha 1-adrenoceptor agonist, phenylephrine, did not induce any changes in these parameters. A marked insulin release following the injection of a maximal dose of the beta 2-adrenoceptor agonist, terbutaline, was accompanied by an increase (30-50%) in islet monoamine oxidase activity. The largest increase in monoamine oxidase activity was observed with serotonin as substrate (50%). These effects on insulin secretion and monoamine oxidase activity could not be blocked by clonidine. Similarly, injection of the non-selective alpha-adrenoceptor agonist, adrenaline, which unlike clonidine does not penetrate the blood-brain barrier, had no effect on insulin release induced by a maximal dose of the nonselective beta-adrenoceptor agonist, isoprenaline. Adrenaline, however, markedly suppressed the insulin release induced by a maximal dose of glucose. Cholinergic muscarinic stimulation by a maximal insulin releasing dose of carbachol did not affect islet monoamine oxidase activity. The results suggest that beta 2-adrenoceptor stimulation of islet monoamine oxidase activity reduced the monoamine content and thereby facilitated the release of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Panagiotidis
G
G
Department of Pharmacology, University of Lund, Sweden.
Stenström
A
A
Lundquist
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D013379:Substrate Specificity; D013726:Terbutaline / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D007328:Insulin; D008995:Monoamine Oxidase; D003000:Clonidine; D013726:Terbutaline