ArticleNature2019
Habenular TCF7L2 links nicotine addiction to diabetes.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 3 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- Risk Factors for First-Ever Diabetes-Related Foot Ulcer: A Systematic Review and Meta-Analysis.International wound journal · 2025Pooled it
- Smoking Status and Type 2 Diabetes, and Cardiovascular Disease: A Comprehensive Analysis of Shared Genetic Etiology and Causal Relationship.Frontiers in endocrinology · 2022Pooled it
- Pooled it
- Joint effect of nicotine use and diabetes distress on glycemic control in young adults with type 1 diabetes.Journal of diabetes and its complications · 2025Trial
- Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).Cardiovascular diabetology · 2022Trial
- [Smoking and nicotine use, heated tobacco products, psychological and socioeconomic aspects of dependence, alcohol, infections, vaccination and diabetes mellitus (Update 2026)].Wiener klinische Wochenschrift · 2026Review
- Revisiting food addiction in the era of GLP-1-based obesity pharmacotherapy via neural reward pathways linking feeding and substance use.Frontiers in behavioral neuroscience · 2026Review
- Neural Regulation of Blood Glucose in Acute Stress: A Report on Research Supported by Pathway to Stop Diabetes.Diabetes · 2026Review
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- Fundamental role of brain-organ interaction in behavior-driven holistic homeostasis.Fundamental research · 2025Review
- Nicotine Reprograms Aging-Related Metabolism and Protects Against Motor Decline in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Gene-Smoking Interaction in Insulin Sensitivity and β-Cell Function Among Normal Glucose Tolerance Individuals.Journal of diabetes · 2025Article
- Shared and unique 3D genomic features of substance use disorders across multiple cell types.medRxiv : the preprint server for health sciences · 2025Article
- The national and provincial prevalence and non-fatal burdens of diabetes in China from 2005 to 2023 with projections of prevalence to 2050.Military Medical Research · 2025Article
- Calcium-activated ion channels drive atypical inhibition in medial habenula neurons.Science advances · 2025Article
- Expression of sensitized β2 nAChR subunits in VTA neurons enhances intravenous nicotine self-administration in male rats.Neuropharmacology · 2024Article
- Neuronal TCF7L2 in Lateral Habenula Is Involved in Stress-Induced Depression.International journal of molecular sciences · 2024Article
- From smoke to stroke: quantifying the impact of smoking on stroke prevalence.BMC public health · 2024Article
- Acute nicotine activates orectic and inhibits anorectic brain regions in rats exposed to chronic nicotine.Neuropharmacology · 2024Article
- Neuroscience in addiction research.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
Diabetes is far more prevalent in smokers than non-smokers, but the underlying mechanisms of vulnerability are unknown. Here we show that the diabetes-associated gene Tcf7l2 is densely expressed in the medial habenula (mHb) region of the rodent brain, where it regulates the function of nicotinic acetylcholine receptors. Inhibition of TCF7L2 signalling in the mHb increases nicotine intake in mice and rats. Nicotine increases levels of blood glucose by TCF7L2-dependent stimulation of the mHb. Virus-tracing experiments identify a polysynaptic connection from the mHb to the pancreas, and wild-type rats with a history of nicotine consumption show increased circulating levels of glucagon and insulin, and diabetes-like dysregulation of blood glucose homeostasis. By contrast, mutant Tcf7l2 rats are resistant to these actions of nicotine. Our findings suggest that TCF7L2 regulates the stimulatory actions of nicotine on a habenula-pancreas axis that links the addictive properties of nicotine to its diabetes-promoting actions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.