Interactions between cholinergic agonists and enteric factors in the regulation of insulin secretion from isolated...

The ability of the cholinergic agonist carbachol to sensitize islets to the action of combined glucose, cholecystokinin and gastric inhibitory polypeptide was determined in isolated rat islets. In response to this combination, peak first phase insulin secretion from control islets averages 85 +/- 5 pg.islet-1.min-1 (mean +/- SEM) and the insulin secretory rates measured 35-40 min after the onset of stimulation averages 127 +/- 34 pg.islet-1.min-1. A prior 20 min exposure to 1 mmol/l carbachol potentiates the modest insulin stimulatory response to this combination of stimulants: peak first phase release is 354 +/- 61 pg.islet-1.min-1, and release measured 35-40 min after the onset of stimulation is 179 +/- 34 pg.islet-1.min-1. This sensitizing effect of carbachol lasts for at least 40 min and can be duplicated by the natural in vivo agonist acetylcholine. These results demonstrate that cholinergic stimulation of isolated islets primes them to the subsequent stimulatory effect of a moderate increase in the circulating glucose level and to several postulated incretin factors. If operative in vivo, this communications network between cephalic and enteric factors represents a remarkable control system to ensure the release of insulin in amounts commensurate to meet the anticipated and actual insulin requirements for insulin-mediated fuel disposition.