Nicotine increases diabetes risk: Should we reconsider patches?
Nicotine binds to and activates nicotinic acetylcholine receptors (nAchRs) known to respond to the neurotransmitter acetylcholine. Accumulating evidence suggests that long-term exposure to nicotine desensitises nAchRs and impairs pancreatic beta cell function and insulin secretion, resulting in an increased risk of type 2 diabetes. However, the underlying mechanism is poorly understood.
Insight into the mode of action of nicotine
The NACHO project wished to shed light into the mechanisms by which nicotine modulates beta cell function under physiological and metabolically compromised conditions. The research was undertaken with the support of the Marie Skłodowska-Curie programme and consisted of a series of in vitro and animal experiments that aimed to delineate how nicotine modulates insulin secretion. As Isabella Artner, Senior Lecturer at Lund University in Sweden explains: “We employed human donor pancreatic islets to assess how short-term nicotine exposure effects insulin secretion, and animal models to assess long-term nicotine effects.” Following exposure to nicotine, scientists evaluated various cell signalling responses, such as mitochondrial activity and calcium influx, key molecular events during glucose-mediated insulin secretion. They also assessed beta cell function, as well as proliferation in vivo (glucose tolerance) and ex vivo (insulin secretion). Results showed that in vivo long-term exposure to nicotine severely impairs insulin secretion by intervening with the communication between the autonomic nervous system and pancreatic beta cells. This also blocks nicotinic signalling during beta cell development, hampering the formation of islets of Langerhans and of connections with nerve cells.
The impact of NACHO research
Researchers plan to transition the animal experiments by using human induced pluripotent stem cells. They aim to determine if there is a direct effect of nicotine exposure on human beta cell clustering and islet formation. Nonetheless, the results are expected to have important socioeconomic ramifications given that diabetes affects hundreds of millions of individuals worldwide and causes millions of deaths every year. According to Artner: “The uniqueness of our project is that contrary to previous studies which had focused on determining if nicotine affected insulin secretion in response to glucose, NACHO investigated the connection of nicotine with parasympathetic stimulation.” Loss of parasympathetic stimulation has been reported as a risk factor for type 2 diabetes development, and the NACHO results suggest that nicotine exposure - which is also a risk factor for type 2 diabetes - is implicated in the mechanism. As a result, understanding how nicotine influences beta cell function in diabetes development is of considerable clinical interest since tobacco abuse is common. “Importantly, the finding that nicotine impairs islet formation could explain why children exposed to maternal smoking have a higher risk of developing diabetes,” emphasises Artner. This also highlights the importance of public health smoking prevention programmes, especially for women at childbearing age. Furthermore, nicotine treatment warrants further investigation as a safe smoking cessation approach. When it comes to diabetes treatment, insulin injections cannot prohibit diabetes-associated long-term complications. Adoptive cell transfer of pancreatic beta cells has thus been proposed as an alternative treatment strategy that requires, however, large numbers of functional beta cells. NACHO results provide significant insight into the complex mechanisms underlying the normal development of beta cells and may help optimise their transplantation.
Keywords
NACHO, nicotine, diabetes, insulin secretion, pancreatic beta cells, nervous system, islets