22nd October 2019. 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.
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
“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.”
Institute on Drug Abuse (NIDA) is a component of the National Institutes of
Health, U.S. Department of Health and Human Services.
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.
TCF7L2 links nicotine addiction to diabetes” is published in “Nature”
– International Journal of Science.
Team of researchers is comprised with Alexander Duncan, Mary P. Heyer, Masago Ishikawa, Stephanie P. B. Caligiuri, Xin-an Liu, Zuxin Chen, Maria Vittoria Micioni Di Bonaventura, Karim S. Elayouby, Jessica L. Ables, William M. Howe, Purva Bali, Clementine Fillinger, Maya Williams, Richard M. O’Connor, Zichen Wang, Qun Lu, Theodore M. Kamenecka, Avi Ma’ayan, Heidi C. O’Neill, Ines Ibanez-Tallon, Aron M. Geurts & Paul J. Kenny.
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