Smoke Signals: Study Shows Path Linking Nicotine Addiction to Increased Risk for Diabetes
Arthur T Knackerbracket has found the following story:
Researchers from the Icahn School of Medicine at Mount Sinai have discovered a circuit in rats that links cigarette smoking and the risk of developing type 2 diabetes, according to a study featured on the cover of the October 17 issue of Nature.
Diabetes is far more prevalent in smokers than non-smokers, but the reasons why have remained unknown until now. The researchers showed that consumption of nicotine is linked, through a brain circuit, to the activity of the pancreas. Nicotine use leads the pancreas to release less insulin, which raises the level of blood sugar; higher levels of blood sugar are associated with a higher risk of diabetes.
Specifically, the researchers found that a protein encoded by a diabetes-related gene called transcription factor 7 like 2 (Tcf7l2) mediates a signaling circuit that connects neurons in the brain activated by nicotine to blood-glucose regulation by the pancreas. The nicotine activates nicotine acetylcholine receptor (nAChR) proteins expressed on neurons in the medial habenula (a brain area that regulates aversive reactions to nicotine), leading to adverse responses to nicotine that limit both intake and the release of glucagon and insulin by the pancreas. This, in turn, raises the levels of blood sugar, and the raised levels of blood sugar create a feedback loop by inhibiting the nAChR-expressing neurons, blocking adverse responses to smoking and so helping to establish nicotine dependence. Tcf7l2 modulates the entire signaling circuit, thereby linking nicotine addiction with an increased risk of diabetes.
"Our findings are important because they describe a mechanism that controls the addictive properties of nicotine and, surprisingly, show that the same addiction-related brain circuits also contribute to smoking-related diseases previously thought to be related to the actions of tobacco outside the brain," says Paul J. Kenny, PhD, Ward-Coleman Professor and Chair of the Nash Family Department of Neuroscience at the Icahn School of Medicine at Mount Sinai and senior author of the paper. "These unexpected findings suggest that at least some of the disease-causing actions of nicotine arise in the brain by the very same circuits that control the addictive properties of the drug. This means that the addictive and disease-causing actions of tobacco may, in some cases, share the very same underlying mechanisms."
Journal Reference:
Alexander Duncan, Mary P. Heyer, et al. Habenular TCF7L2 links nicotine addiction to diabetes. Nature, 2019; 574 (7778): 372 DOI: 10.1038/s41586-019-1653-x
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