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 β-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 μmol/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 [3H]nicotine was demonstrated in rat islets and in a β-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 α2, α3, α4, α5, α7, and β2 was detected in INS-1 cells by reverse transcriptase polymerase chain reaction. Acute exposure to cytisine (10−6 mol/L), an agonist of α4, β2 subunits, partially inhibited tolbutamide-induced insulin release. Specific binding of α bungarotoxin (10−10 mol/L), an antagonist of the α7 subunit, could be demonstrated in INS-1 cells, and culture with α 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 β cells.