Cholinergic agonists prime the beta-cell to glucose stimulation.
The ability of the cholinergic agonists carbachol or acetylcholine to stimulate insulin release, activate phosphoinositide hydrolysis, and prime the beta-cell to the insulin stimulatory effect of 7.5 mM glucose was assessed. In the presence of 7 mM glucose, but not 2.75 mM glucose, 1 mM carbachol evoked a sustained insulin secretory response. At both glucose levels, carbachol stimulated phosphoinositide hydrolysis, an event monitored in myo-[2-3H]inositol-prelabeled islets by increases in [3H]inositol efflux and labeled inositol phosphate accumulation. Prior exposure to carbachol (0.1-1 mM) resulted in a dose-dependent increase in the subsequent insulin secretory response to 7.5 mM glucose. This sensitization developed within 2 min and lasted for at least 45 min after carbachol removal from the perifusion medium. Carbachol pretreatment also sensitized the islet to either 200 microM tolbutamide or 10 mM arginine. Prior exposure to 1 mM acetylcholine induced a similar proemial sensitization to a subsequent challenge with glucose. These results demonstrate that even though cholinergic stimulation increases phosphoinositide hydrolysis, this event is insufficient to initiate sustained insulin secretion from islets exposed to a low (2.75 mM) glucose concentration. However, this increase in phosphoinositide hydrolysis sensitizes islets to a subsequent challenge with one of several different stimuli, including glucose. Hence, this sensitization of islets to physiologically relevant glucose concentrations may represent the major contribution of vagal stimulation to the regulation of insulin secretion.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, Connecticut 06536-0740.
Zawalich
K C
KC
Rasmussen
H
H
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology*; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology
D007295:Inositol Phosphates; D007328:Insulin; D007294:Inositol; D001285:Atropine; D002217:Carbachol; D001120:Arginine; D014044:Tolbutamide; D005947:Glucose