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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 (1 μM) 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. -- Highlights: ► Smoking cessation drugs have the potential to disrupt betamore » cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.« less

Authors:
 [1];  [2];  [1];  [1]
  1. Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada L8N 3Z5 (Canada)
  2. Department of Pediatrics, McMaster University, Hamilton, ON, Canada L8N 3Z5 (Canada)
Publication Date:
OSTI Identifier:
22215981
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 265; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABLATION; ACETYLCHOLINE; CHEMOTHERAPY; CONCENTRATION RATIO; ENZYME ACTIVITY; GLUCOSE; IN VITRO; IN VIVO; INSULIN; MITOCHONDRIA; NICOTINE; OXIDATION; PANCREAS; RATS; RECEPTORS; SMOKES

Citation Formats

Woynillowicz, Amanda K., Raha, Sandeep, Nicholson, Catherine J., and Holloway, Alison C., E-mail: hollow@mcmaster.ca. The effect of smoking cessation pharmacotherapies on pancreatic beta cell function. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.020.
Woynillowicz, Amanda K., Raha, Sandeep, Nicholson, Catherine J., & Holloway, Alison C., E-mail: hollow@mcmaster.ca. The effect of smoking cessation pharmacotherapies on pancreatic beta cell function. United States. doi:10.1016/J.TAAP.2012.08.020.
Woynillowicz, Amanda K., Raha, Sandeep, Nicholson, Catherine J., and Holloway, Alison C., E-mail: hollow@mcmaster.ca. Thu . "The effect of smoking cessation pharmacotherapies on pancreatic beta cell function". United States. doi:10.1016/J.TAAP.2012.08.020.
@article{osti_22215981,
title = {The effect of smoking cessation pharmacotherapies on pancreatic beta cell function},
author = {Woynillowicz, Amanda K. and Raha, Sandeep and Nicholson, Catherine J. and Holloway, Alison C., E-mail: hollow@mcmaster.ca},
abstractNote = {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 (1 μM) 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. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.},
doi = {10.1016/J.TAAP.2012.08.020},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 265,
place = {United States},
year = {2012},
month = {11}
}