ArticleNature medicine2015
Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Comparison of the health-related outcomes for traditional cigarettes, e-cigarettes, heat-not-burn cigarettes and snus: a systematic review and meta-analysis.BMC public health · 2026Pooled it
- The association between smoking and diabetic neuropathy: a systematic review and meta-analysis.Systematic reviews · 2025Pooled it
- Pooled it
- Cordycepin alleviates nicotine withdrawal-induced anxietyDrug and alcohol dependence reports · 2026Article
- Adipose extracellular vesicles carrying miR-210-3p drive macrophage inflammation and nicotine-induced atherosclerosis.iScience · 2026Article
- Smoking, GAD65 autoimmunity, genetic susceptibility to type 1 diabetes and incident adult-onset diabetes in the EPIC-InterAct case-cohort study.Metabologia · 2026Article
- C1q/TNF-Related Protein 4 (C1QTNF4) Acts as an Adipokine That Ameliorates Diet-Induced Obesity by Improving Energy Metabolism and Alleviating Adipose Inflammation.Mediators of inflammation · 2026Article
- Investigating the Link Between Smoking and Fatty Liver via Ultrasound Elastography: A Cross-Sectional Analysis Study.Canadian journal of gastroenterology & hepatology · 2026Article
- Nicotine Reprograms Aging-Related Metabolism and Protects Against Motor Decline in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Association between e-cigarette smoking and insulin resistance using the triglyceride-glucose index in Korean adults: Korea National Health and Nutrition Examination Survey.Korean journal of family medicine · 2025Article
- Gene-Smoking Interaction in Insulin Sensitivity and β-Cell Function Among Normal Glucose Tolerance Individuals.Journal of diabetes · 2025Article
- Cigarette Smoke Contributes to the Progression of MASLD: From the Molecular Mechanisms to Therapy.Cells · 2025Review
- Adipose tissue dysfunction disrupts metabolic homeostasis: mechanisms linking fat dysregulation to disease.Frontiers in endocrinology · 2025Review
- Smoking, Obesity, and Post-Cessation Weight Gain: Neurobiological Intersection and Treatment Recommendations.Journal of multidisciplinary healthcare · 2025Review
- Interplay of Oxidative Stress, Gut Microbiota, and Nicotine in Metabolic-Associated Steatotic Liver Disease (MASLD).Antioxidants (Basel, Switzerland) · 2024Review
- Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds.Current nutrition reports · 2024Review
- Acute nicotine intake increases feeding behavior through decreasing glucagon signaling in dependent male and female rats.Hormones and behavior · 2024Article
- Article
- Gut microbial metabolites reveal diet-dependent metabolic changes induced by nicotine administration.Scientific reports · 2024Article
- A retrospective evaluation of parental smoking and the risk of Type 1 diabetes in children.Tobacco induced diseases · 2024Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Cigarette smoking promotes body weight reduction in humans while paradoxically also promoting insulin resistance (IR) and hyperinsulinemia. However, the mechanisms behind these effects are unclear. Here we show that nicotine, a major constituent of cigarette smoke, selectively activates AMP-activated protein kinase α2 (AMPKα2) in adipocytes, which in turn phosphorylates MAP kinase phosphatase-1 (MKP1) at serine 334, initiating its proteasome-dependent degradation. The nicotine-dependent reduction of MKP1 induces the aberrant activation of both p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, leading to increased phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307. Phosphorylation of IRS1 leads to its degradation, protein kinase B inhibition, and the loss of insulin-mediated inhibition of lipolysis. Consequently, nicotine increases lipolysis, which results in body weight reduction, but this increase also elevates the levels of circulating free fatty acids and thus causes IR in insulin-sensitive tissues. These results establish AMPKα2 as an essential mediator of nicotine-induced whole-body IR in spite of reductions in adiposity.
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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.