Evidence for functional nicotinic receptors on pancreatic β cells

Epidemiological studies associate smoking with reduced insulin secretion. We hypothesized that nicotine could negatively affect pancreatic beta-cell function. Acute or 48-hour exposures to nicotine (10(-4) to 10(-6) mol/L) moderately inhibited insulin release at basal (3.3 mmol/L) and/or elevated (27 mmol/L) glucose in rat and human islets. Acute exposure to nicotine (10-6 mol/L) inhibited tolbutamide (200 mumol/L)-induced insulin release by 41% (P < .05), but did not affect secretion induced by KCl (20 mmol/L) or 3-isobutyl-1-methylxanthine (1 mmol/L) (tested in rat islets). Specific binding of [H-3]nicotine was demonstrated in rat islets and in a beta-cell line of rat origin, INS-1. Such binding was enhanced by 48 hours of coculture with nicotine (10(-7) mol/L). Expression of mRNA for the nicotinic receptor subunits alpha2, alpha3, alpha4, alpha5, alpha7, and beta2 was detected in INS-1 cells by reverse transcriptase polymerase chain reaction. Acute exposure to cytisine (10(-6) mol/L), an agonist of alpha4, beta2 subunits, partially inhibited tolbutamide-induced insulin release. Specific binding of 1 bungarotoxin (10(-10) mol/L), an antagonist of the a7 subunit, could be demonstrated in INS-1 cells, and culture with a bungarotoxin modestly increased insulin release in postculture incubations at basal and elevated glucose, P < .05. Our data indicate that functional nicotinic receptors are present in pancreatic islets and beta cells. (C) 2005 Elsevier Inc. All rights reserved.