Evidence for functional nicotinic receptors on pancreatic beta 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 micromol/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 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 alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, and beta 2 was detected in INS-1 cells by reverse transcriptase polymerase chain reaction. Acute exposure to cytisine (10(-6) mol/L), an agonist of alpha 4, beta 2 subunits, partially inhibited tolbutamide-induced insulin release. Specific binding of alpha bungarotoxin (10(-10) mol/L), an antagonist of the alpha 7 subunit, could be demonstrated in INS-1 cells, and culture with alpha 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.
Yoshikawa
Hiroyasu
H
Endocrine Section, Department of Medicine, Norwegian University of Science and Technology, Trondheim N-7489, Norway.
Hellström-Lindahl
Ewa
E
Grill
Valdemar
V
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D000093843:Quinolizidine Alkaloids
D000255:Adenosine Triphosphate; D000470:Alkaloids; D001392:Azocines; D002038:Bungarotoxins; D007328:Insulin; D009538:Nicotine; D018722:Nicotinic Agonists; D011807:Quinolizines; D012313:RNA; D011978:Receptors, Nicotinic; D013778:Tetrazolium Salts; D013844:Thiazoles; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C022616:thiazolyl blue