ReviewFrontiers of medicine2021
Mechanism of insulin resistance in obesity: a role of ATP.
Review in Frontiers of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Adipocyte Size, Overweight, and Insulin Resistance in Type 2 Diabetes Mellitus and the Impact of Weight Loss: A Systematic Review.Nutrients · 2026Pooled it
- FMolecular biology reports · 2023Pooled it
- Associations between multiple air pollutants and insulin resistance in Chinese adults: the moderating role of physical activity.BMC public health · 2026Article
- Changes in Insulin Resistance with Different Weight Loss Methods in Patients with Type Two Diabetes Mellitus and Hypertension: A Comparative Clinical Trial.Journal of clinical medicine · 2026Article
- Myometrial smooth muscle KATP channel activity is attenuated in a mouse model of diet-induced obesity during pregnancy†.Biology of reproduction · 2025Article
- Connecting the Dots: Mitochondrial Dysfunction, PCOS, and Insulin Resistance-Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- The Diabetogenic Effect of Statin Use May Interact With Polygenic Risk Scores for Type 2 Diabetes: Evidence From the UK Biobank.Journal of preventive medicine and public health = Yebang Uihakhoe chi · 2025Article
- 4'-Methoxyresveratrol Improves Hepatic Insulin Resistance Induced by a High-Fat-Diet via Anti-Oxidative-Stress Activity.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Estimated glucose disposal rate mediates the association between Life's Crucial 9 and congestive heart failure: a population-based study.Frontiers in endocrinology · 2025Article
- Type 2 diabetes: a sacrifice program handling energy surplus.Life metabolism · 2024Review
- mTOR Dysregulation, Insulin Resistance, and Hypertension.Biomedicines · 2024Review
- Melatonin Alleviates Liver Mitochondrial Dysfunction in Leptin-Deficient Mice.International journal of molecular sciences · 2024Article
- Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus.Acta pharmaceutica Sinica. B · 2024Review
- Prevalence, associated factors, and gene polymorphisms of obesity in Tibetan adults in Qinghai, China.BMC public health · 2024Article
- TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet.Cell reports · 2024Article
- Association between systemic immune-inflammation index and insulin resistance and mortality.Scientific reports · 2024Article
- Effect of Hydrogen Sulfide on Sympathoinhibition in Obese Pithed Rats and Participation of KInternational journal of hypertension · 2024Article
- Article
- Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration.Research (Washington, D.C.) · 2024Article
- Acupoint catgut embedding: a potential intervention strategy for obesity-related precocious puberty.Frontiers in endocrinology · 2024Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named "mitochondrial overheating." Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.
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