Evidence for differential effects of noradrenaline and somatostatin on intracellular messenger systems in rat islets of Langerhans.
The mechanisms involved in inhibition of insulin secretion by somatostatin and noradrenaline were compared in order to establish whether the receptors for these agents are coupled to similar effector systems in the pancreatic B cell. Both agents significantly reduced forskolin-induced adenylate cyclase activity in islet homogenates, although noradrenaline was more effective than somatostatin. The capacity of noradrenaline to inhibit insulin secretion was largely unaffected by agents that increase intracellular cyclic AMP, whereas the effect of somatostatin as an inhibitor was markedly reduced under these conditions. Both noradrenaline and somatostatin inhibited the stimulation of insulin secretion induced by K+ depolarization, but different mechanism were involved. Somatostatin significantly inhibited K(+)-stimulated 45Ca2+ efflux and influx in islets, while noradrenaline exerted only a minor influence on these processes. The data indicate that noradrenaline controls insulin secretion by a mechanism which operates beyond the level of intracellular messenger generation. In contrast, somatostatin exerts at least part of its inhibitory effect on insulin secretion by directly controlling islet cell Ca2+ influx in a manner which may be regulated by cyclic AMP.
Hurst
R D
RD
Department of Biological Sciences, University of Keele, Staffordshire.
Morgan
N G
NG
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors
D007328:Insulin; D005576:Colforsin; D013004:Somatostatin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine