Nicotine addiction linked to diabetes through a DNA-regulating gene in animal models

Researchers have discovered a mechanism in rats that links cigarette smoking and the risk of developing type 2 diabetes. Scientists found a crucial role for a diabetes-associated gene, called transcription factor 7-like 2 (Tcf7l2), in regulating the response to nicotine in the brain. Tcf712, which regulates the expression of genes in the pancreas and liver that determine blood glucose levels, also regulates the response of cells in the habenula, an area of the brain that controls reward and aversion behaviors, to nicotine. Variation in Tcf7l2 increases the risk of developing type 2 diabetes, but little has been known about its function in the brain. The study discovered that Tcf712 controls a pathway linking the habenula, which controls nicotine intake, to the pancreas, with this circuit responsible for nicotine-induced increases in blood glucose.

To investigate the association between Tcf7l2, nicotine addiction and blood glucose regulation, researchers genetically deleted Tcf7l2, in rats. The mutant rats consumed much greater quantities of nicotine at each dose. Unexpectedly, while the loss of Tcf7l2 function in the habenula increased nicotine consumption in rats, this change also reduced nicotine-driven blood glucose increases and protected against the emergence of diabetes-associated abnormalities in blood glucose levels.

“This unanticipated finding suggests a link between nicotine use and the onset of type 2 diabetes, with implications for future prevention and treatment strategies for both diseases” said NIDA Director Dr. Nora D. Volkow. “Although addiction is a brain disease, this discovery underscores how the body’s complex functions are exquisitely interconnected, revealing the need for integrated and innovative research.”

If these findings in rats extend to human cigarette smokers, they suggest a complex dynamic in which variations in the Tcf7l2 gene might influence both the risk of tobacco addiction and the development of tobacco-associated type 2 diabetes. More broadly, these findings suggest that type 2 diabetes – and perhaps other cigarette smoking-related diseases in which abnormalities in the autonomic nervous system play a role, such as hypertension and cardiovascular disease – originate in the brain and implicate nicotine-induced disrupted interactions between the habenula and the peripheral nervous system.

For more information about nicotine and smoking, visit: Tobacco/Nicotine and E-Cigs.

For more information, contact the NIDA press office at media@nida.nih.gov or 301-443-6245. Follow NIDA on Twitter and Facebook.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

About the National Institute on Drug Abuse (NIDA): The National Institute on Drug Abuse (NIDA) is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. Fact sheets on the health effects of drugs and information on NIDA research and other activities can be found at www.drugabuse.gov, which is now compatible with your smartphone, iPad or tablet. To order publications in English or Spanish, call NIDA’s DrugPubs research dissemination center at 1-877-NIDA-NIH or 240-645-0228 (TDD) or email requests to drugpubs@nida.nih.gov. Online ordering is available at drugpubs.drugabuse.gov. NIDA’s media guide can be found at www.drugabuse.gov/publications/media-guide/dear-journalist, and its easy-to-read website can be found at www.easyread.drugabuse.gov. You can follow NIDA on Twitter and Facebook.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.