ArticleEndocrinology2012
AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol.
Article in Endocrinology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed.
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- What Is Cardiometabolic HFpEF and How Can We Study it Preclinically?JACC. Basic to translational science · 2025Review
- Exploring the therapeutic potential of extract in targeting localized adiposity.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Cargo-selective regulation of clathrin-mediated endocytosis by AMP-activated protein kinase.iScience · 2025Article
- Comparative advantage and efficacy of natural products for polycystic ovary syndrome.Journal of ovarian research · 2025Review
- Flavonoids of Mao Jian Green Tea Ameliorate Glycemic Metabolism in Type-2-Diabetic Rats via AMPK Signaling Pathways and Gut Microbiota Regulation.Foods (Basel, Switzerland) · 2025Article
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- Aspects of β-sitosterol's Pharmacology, Nutrition and Analysis.Current pharmaceutical biotechnology · 2025Review
- The protective effect of Saudi Arabian bee honey against excessive weight gain and obesity-related parameters in rats fed a high-fat diet.Frontiers in nutrition · 2025Article
- Ferulic acid improves palmitate-induced insulin resistance by regulating IRS-1/Akt and AMPK pathways in L6 skeletal muscle cells.Toxicology research · 2024Article
- Ischemic Stroke and the Biological Hallmarks of Aging.Aging and disease · 2024Review
- Alterations of whole body glucose metabolism in a feline SARS-CoV-2 infection model.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- A critical review of ethanol effects on neuronal firing: A metabolic perspective.Alcohol, clinical & experimental research · 2024Review
21 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
Abstract
AMP-activated protein kinase (AMPK) enhances glucose transporter GLUT4 regulation. AMPK also suppresses energy-consuming pathways such as cholesterol synthesis. Interestingly, recent in vitro and in vivo data suggest that excess membrane cholesterol impairs GLUT4 regulation. Therefore, this study tested whether a beneficial, GLUT4-regulatory aspect of AMPK stimulation involved cholesterol lowering. Using L6 myotubes stably expressing an exofacial myc-epitope-tagged-GLUT4, AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR; 45 min, 1 mm) or 2,4-dinitrophenol (DNP; 30 min, 200 μm) increased cell surface GLUT4myc labeling by approximately ≈ 25% (P < 0.05). Insulin (20 min, 100 nm) also increased GLUT4myc labeling by about 50% (P < 0.05), which was further enhanced (≈ 25%, P < 0.05) by AICAR or DNP. Consistent with AMPK-mediated suppression of cholesterol synthesis, AICAR and DNP decreased membrane cholesterol by 20-25% (P < 0.05). Whereas AMPK knockdown prevented the enhanced basal and insulin-stimulated GLUT4myc labeling by AICAR and DNP, cholesterol replenishment only blocked the AMPK-associated enhancement in insulin action. Cells cultured in a hyperinsulinemic milieu, resembling conditions in vivo that promote the progression/worsening of insulin resistance, displayed an increase in membrane cholesterol. This occurred concomitantly with a loss of cortical filamentous actin (F-actin) and defects in GLUT4 regulation by insulin. These derangements were prevented by AMPK stimulation. Examination of skeletal muscle from insulin-resistant Zucker rats revealed a similar elevation in membrane cholesterol and loss of F-actin. Lowering cholesterol to control levels restored F-actin structure and insulin sensitivity. In conclusion, these data suggest a novel aspect of GLUT4 regulation by AMPK involves membrane cholesterol lowering. Moreover, this AMPK-mediated process protected against hyperinsulinemia-induced insulin resistance.
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