title: The effect of smoking cessation pharmacotherapies on pancreatic beta cell function.
abstract: The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1μM) of three test compounds resulted in an ablation of normal glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation.
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada L8N 3Z5. jeta@kemi.dtu.dk
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Woynillowicz
authors.forename: Sandeep
authors.initials: S
authors.lastname: Raha
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Nicholson
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000633:toxicity; D016642:Bupropion / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D004579:Electron Transport / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010186:Pancreatic Function Tests; D011810:Quinoxalines / Q000633:toxicity; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000188:drug therapy*; D016540:Smoking Cessation; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D007328:Insulin; D018722:Nicotinic Agonists; D011810:Quinoxalines; D016642:Bupropion; D009538:Nicotine; D005947:Glucose; D000068580:Varenicline