ArticleJournal of cellular and molecular medicine2017
Excess cholesterol inhibits glucose-stimulated fusion pore dynamics in insulin exocytosis.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.The Journal of clinical investigation · 2024Trial
- Dapansutrile preserves pancreatic beta-cell function by regulating insulin vesicle membrane fusion and mitochondrial homeostasis.Diabetes, obesity & metabolism · 2026Article
- Associations between metabolic disorders and Sjögren's disease.The Japanese dental science review · 2024Review
- Association of remnant cholesterol and newly diagnosed early-onset type 2 diabetes mellitus in Chinese population: A retrospective cross-sectional study.Journal of diabetes · 2024Article
- Palmitoylation couples insulin hypersecretion with β cell failure in diabetes.Cell metabolism · 2023Article
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Association between preoperative lipid profiles and new-onset diabetes after transplantation in Chinese kidney transplant recipients: A retrospective cohort study.Journal of clinical laboratory analysis · 2021Article
- MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus.Biology · 2021Review
- Exocytotic fusion pore under stress.Cell stress · 2020Review
- Article
- Role of High-Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control.Journal of the American Heart Association · 2020Review
- Phosphatidylinositol-4,5-Biphosphate (PI(4,5)PBioMed research international · 2020Article
- The PI(4)P phosphatase Sac2 controls insulin granule docking and release.The Journal of cell biology · 2019Article
- A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion.International journal of molecular medicine · 2019Article
- RCAN1 Knockdown Reverts Defects in the Number of Calcium-Induced Exocytotic Events in a Cellular Model of Down Syndrome.Frontiers in cellular neuroscience · 2018Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes is caused by defects in both insulin sensitivity and insulin secretion. Glucose triggers insulin secretion by causing exocytosis of insulin granules from pancreatic β-cells. High circulating cholesterol levels and a diminished capacity of serum to remove cholesterol from β-cells are observed in diabetic individuals. Both of these effects can lead to cholesterol accumulation in β-cells and contribute to β-cell dysfunction. However, the molecular mechanisms by which cholesterol accumulation impairs β-cell function remain largely unknown. Here, we used total internal reflection fluorescence microscopy to address, at the single-granule level, the role of cholesterol in regulating fusion pore dynamics during insulin exocytosis. We focused particularly on the effects of cholesterol overload, which is relevant to type 2 diabetes. We show that excess cholesterol reduced the number of glucose-stimulated fusion events, and modulated the proportion of full fusion and kiss-and-run fusion events. Analysis of single exocytic events revealed distinct fusion kinetics, with more clustered and compound exocytosis observed in cholesterol-overloaded β-cells. We provide evidence for the involvement of the GTPase dynamin, which is regulated in part by cholesterol-induced phosphatidylinositol 4,5-bisphosphate enrichment in the plasma membrane, in the switch between full fusion and kiss-and-run fusion. Characterization of insulin exocytosis offers insights into the role that elevated cholesterol may play in the development of type 2 diabetes.
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