ArticleAutophagy2015
Chronic HMGCR/HMG-CoA reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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
33 citing papers in PubMed, 57 citations in OpenAlex.
- Mechanisms and Predisposing Conditions for Statin-Induced New-Onset Type 2 Diabetes Mellitus: A Paradox Relative to Their Pleiotropic Metabolic Effects.Endocrinology, diabetes & metabolism · 2026Review
- FDFT1 Acts as a Negative Regulator of Autophagy by Modulating AMPK-ULK1 Signaling in Hepatocellular Carcinoma Cells.Biomolecules & therapeutics · 2026Article
- Drug-Induced Glucose Metabolism Disorders: Role of Aryl Hydrocarbon Receptor.Journal of xenobiotics · 2025Review
- Sodium-Glucose Cotransporter-2 Inhibitor Enhances Hepatic Gluconeogenesis and Reduces Lipid Accumulation via AMPK-SIRT1 Activation and Autophagy Induction.Endocrinology and metabolism (Seoul, Korea) · 2025Article
- Corporate genome screening India (CoGsI) identified genetic variants association with T2D in young Indian professionals.Scientific reports · 2025Article
- Autophagy regulates MK-2206-induced LDL receptor expression and cholesterol efflux pathways.PloS one · 2025Article
- Integrated metabolomics and network pharmacology to investigate the anti-hyperlipidemia effect of geniposidic acid on high-fat diet induced mice.Frontiers in cell and developmental biology · 2025Article
- Short-Term Statin Therapy Induces Hepatic Insulin Resistance Through HNF4α/PAQR9/PPM1α Axis Regulated AKT Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Role of Gut Microbiota in Statin-Associated New-Onset Diabetes-A Cross-Sectional and Prospective Analysis of the FINRISK 2002 Cohort.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Review
- Statins and risk of type 2 diabetes: mechanism and clinical implications.Frontiers in endocrinology · 2023Review
- Geranylgeranyl pyrophosphate depletion by statins compromises skeletal muscle insulin sensitivity.Journal of cachexia, sarcopenia and muscle · 2022Article
- DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice.Diabetes & metabolism journal · 2022Article
- Pitavastatin activates mitophagy to protect EPC proliferation through a calcium-dependent CAMK1-PINK1 pathway in atherosclerotic mice.Communications biology · 2022Article
- Therapeutic regulation of autophagy in hepatic metabolism.Acta pharmaceutica Sinica. B · 2022Review
- Undertreatment or Overtreatment With Statins: Where Are We?Frontiers in cardiovascular medicine · 2022Review
- Autophagy in liver diseases: A review.Molecular aspects of medicine · 2021Review
- Drugs Interfering with Insulin Resistance and Their Influence on the Associated Hypermetabolic State in Severe Burns: A Narrative Review.International journal of molecular sciences · 2021Review
- High-Efficacy α,β-Dehydromonacolin S Improves Hepatic Steatosis and Suppresses Gluconeogenesis Pathway in High-Fat Diet-Induced Obese Rats.Pharmaceuticals (Basel, Switzerland) · 2021Article
- New Insights Into the Role of Autophagy in Liver Surgery in the Setting of Metabolic Syndrome and Related Diseases.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Statins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.
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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.