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Volume 574 Issue 7778, 17 October 2019

Smoke signals

Cigarette smoking dramatically increases the risk of type 2 diabetes, but the mechanisms underlying this effect have remained elusive. In a paper in this issue, Paul Kenny and his colleagues reveal that, in rats, the transcription factor TCF7L2 mediates a signalling circuit that connects neurons in the brain activated by nicotine to blood-glucose regulation by the pancreas. The researchers show that when nicotine activates nicotine acetylcholine receptor (nAChR) proteins expressed on neurons in the medial habenula region of the brain, it also leads to adverse responses to nicotine that limit intake as well as to the release of glucagon and insulin by the pancreas. This in turn raises the levels of blood sugar, which is associated with a higher risk of developing diabetes. In addition, the raised levels of blood sugar create a feedback loop by inhibiting nAChRs expressed by medial habenula neurons, blocking adverse responses to smoking and so helping to establish nicotine dependence. TCF7L2 modulates the entire signalling circuit, thereby linking nicotine addiction with an increased risk of diabetes.

Cover image: Ian Tragen.

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