Affiliations : Icahn School of Medicine at Mount Sinai, NY, USA
Journal reference: DOI: 10.1038/s41586-019-1653-x
Summary: Could nicotine addiction be linked to Type II Diabetes? High doses of nicotine have been shown to be linked to increased blood sugar levels. In this article the neuroscience and genetics behind this link is explained.
Context: both nicotine addiction and diabetes can kill you in the worst case
Tobacco smoking is a leading cause of preventable death and is associated with multiple diseases such as lung cancer, chronic obstructive pulmonary disease and asthma. Even non-smokers are impacted with over 800,000 deaths related to secondhand tobacco smoke exposure.
Surprisingly, epidemiologic studies observed that type 2 diabetes (T2D) is higher in smokers than nonsmokers. This type of diabetes also known as insulin resistant impacts adults and is characterized by hyperglycemia (high levels of sugar in the blood) and high levels of glucagon (a hormone that raises the level of glucose and fatty acids in the bloodstream). T2D patients still produce insulin but their body is unable to use it effectively.
Introduction: nicotine addiction and diabetes are linked
Recently, Pr Paul Kenny’s team at Mount Sinai, New-York, discovered the mechanism that links T2D and tobacco smoking.
First, his team reported that high doses of nicotine induce an important increase in blood sucrose levels.
At the brain level: a brain structure called the habenula holds the key to this link
Interestingly, a brain structure called the medial habenula and known to be activated by the same high doses of nicotine and to act as a satiety signal for nicotine, densely expresses a diabetes-associated transcription factor (a protein that turns specific genes on or off) called TCF7L2. Pr. Kenny’s team used a cutting-edge genetic tool (CRISPR) to specifically ablate TCF7L2 in the medial habenula of rodents.
- This genetic ablation was sufficient to block the nicotine-induced increase in sucrose levels. This result was the first evidence suggesting that the MHb can directly impact blood sucrose.
- Moreover, this genetic manipulation also induced a strong increase in nicotine intake, confirming a link between TCF7L2 in the medial habenula and nicotine-related behaviors.
- The team further showed that besides the acute effect of nicotine on sucrose levels, chronic nicotine can disrupt blood glucose homeostasis (the state of steady internal levels) in rodents that still have TCF7L2. This was reflected by elevated fasting blood glucose levels, the core symptoms of diabetes. Noteworthy, rodents in which TCF7L2 was ablated were resistant to this action of nicotine, meaning that the absence of TCF7L2 protected them.
Habenula – pancreas: the brain-body pathway through which nicotine and blood glucose levels interact
Finally, using tracing methods (methods used to visualize connections from their source to their termination), a connection between the medial habenula and the pancreas was identified. This provides a direct link by which the habenula can influence blood glucose homeostasis.
Take home message
These findings suggest that the medial habenula is a key brain region controlling the sucrose homeostasis in response to nicotine intake via a TCF7L2 mechanism.
More broadly, this discovery reveals that a habenula–pancreas axis, regulated by TCF7L2, links heavy nicotine smoking to diabetes. This has important implications not only for our understanding of the etiology of tobacco-related diseases but also in drug discovery. Indeed, this new brain-body mechanism can be a new target for novel therapeutics designed to modulate brain–body communication in T2D and other smoking-related diseases. Furthermore, some treatments used in T2D might also have an impact on nicotine-related behavior, which could help people with nicotine addiction.