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.

Metabolic effects of smoking cessation

“…The results from animal studies and in vitro experiments show that nicotine exposure results in β-cell toxicity 100–102 . In rabbits, high concentrations of nicotine inhibit glucose-induced insulin secretion, whereas low doses stimulate insulin secretion 103 .…”

Smoking and the risk of type 2 diabetes

“…Moreover, given studies suggesting an independent effect of nicotine to perturb glucose homeostasis, it remains to be clarified whether cessation strategies that include nicotine agonists differentially impact long-term changes in glucose homeostasis. Interestingly, in vitro treatment of INS-1 β cells with nicotine, varenicline, and bupropion led to decreased levels of glucose-stimulated insulin secretion with each agent, suggesting that further studies to address these questions are needed [62]. …”

Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite

“…Nicotine may influence b-cell function directly or indirectly via the parasympathetic ganglia. Animal studies and in vitro experiments suggest that nicotine exposure results in functional impairment and loss of b cells (36,37,38). In rabbits, high concentrations of nicotine inhibit glucose-induced insulin secretion, while lower doses stimulated insulin secretion (39).…”