Effects of alpha-adrenoceptor blockade by phentolamine on basal and stimulated insulin secretion in the mouse.
The sympathetic nervous system is known to innervate the pancreatic islets and to have the capability to influence islet hormone release. The effects are, however, complex since the islet nerves contain catecholaminergic as well as peptidergic fibres, and the catecholamines stimulate alpha- as well as beta-adrenoceptors. The present study was undertaken to establish the possible influence of the alpha-adrenoceptors on basal and stimulated insulin secretion under in vivo conditions. The alpha-adrenoceptor blocker phentolamine was injected at various dose levels i.p. to mice and a dose-dependent increase in plasma concentrations of insulin was seen. The maximal plasma insulin levels were observed 10 min after injection and were accompanied by decreased plasma glucose concentrations. Additionally, plasma glucose levels fell in response to phentolamine by an apparent insulin-independent manner, since at the low dose of 2.6 mumol kg-1, plasma glucose levels did decrease without any apparent increase in plasma insulin levels. After injection of a low dose of phentolamine 10 min prior to a rapid i.v. injection of one of four different insulin secretagogues, the following effects on insulin release were observed. Glucose (+55%) and the cholinergic agonist carbachol (+140%) displayed a potentiated insulin secretory response after phentolamine pretreatment, whereas the beta 2-adrenoceptor agonist terbutaline (-45%) had a blunted, though not abolished, insulin response. The absolute insulin secretory response to CCK-8 was unaffected by phentolamine despite the fact that plasma glucose levels were lowered by phentolamine. In conclusion, phentolamine enhanced insulin secretion and depressed plasma glucose levels in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Ahrén
B
B
Lundquist
I
I
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D008815:Mice, Inbred Strains; D010646:Phentolamine / Q000494:pharmacology*; D013726:Terbutaline / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D013758:Tetragastrin; D002217:Carbachol; D005947:Glucose; D013726:Terbutaline; D010646:Phentolamine