Researchers have found a diabetes-associated gene, called transcription factor 7-like 2 (Tcf7l2) that regulates the response to nicotine in the brain. Tcf7l2 is responsible for regulating the expression of genes in the pancreas and liver that determines blood glucose levels and the response of cells in the habenula.
The study found that Tcf7l2 controls a pathway linking to habenula, which is an area of the brain that controls reward and aversion behaviors. This pathway controls nicotine intake to the pancreas, being responsible for nicotine-induced increases in blood glucose.
Investigators genetically deleted Tcf7l2 in rats to further analyze nicotine addiction and blood glucose regulation, where they saw the rats consume much greater quantities of nicotine at each dose. While the loss of Tcf7l2 function in the habenula increased nicotine consumption in rats, it also reduced nicotine-driven blood glucose increases and protected against the emergence of diabetes-associated abnormalities in blood glucose levels.
These findings suggest that human cigarette smokers might possess a variation in the Tcf7l2 gene that influences both the risk of tobacco addiction and the development of tobacco-associated type 2 diabetes. In addition, these results suggest that type 2 diabetes originate in the brain and implicate nicotine-induced disrupted interactions between the habenula and the peripheral nervous system.
Nicotine addiction linked to diabetes through a DNA-regulating gene in animal models. NIH website. https://www.nih.gov/news-events/news-releases/nicotine-addiction-linked-diabetes-through-dna-regulating-gene-animal-models. Published October 16, 2019. Accessed October 18, 2019.