ArticleMolecular biology of the cell2018
Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP.
Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- ABCA1 as a Gatekeeper of Pancreatic β-Cell Cholesterol Homeostasis: Links Between Lipoprotein Stress, Lipotoxicity, and Insulin Secretion.Nutrients · 2026Review
- From cholesterol to glucose: uncovering how statins induce β-cell dysfunction to promote type 2 diabetes.The Journal of endocrinology · 2025Review
- Review
- Membrane lipids couple synaptotagmin to SNARE-mediated granule fusion in insulin-secreting cells.Molecular biology of the cell · 2024Article
- An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles.Journal of extracellular vesicles · 2023Article
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Adaptation to chronic ER stress enforces pancreatic β-cell plasticity.Nature communications · 2022Article
- Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production.Biomolecules · 2022Review
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Sending out molecules from the TGN.Current opinion in cell biology · 2021Review
- Uncurtaining the pivotal role of ABC transporters in diabetes mellitus.Environmental science and pollution research international · 2021Review
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2.eLife · 2020Article
- The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis.Molecular metabolism · 2020Article
- Ghrelin suppresses migration of macrophages via inhibition of ROCK2 under chronic intermittent hypoxia.The Journal of international medical research · 2020Article
- The PI(4)P phosphatase Sac2 controls insulin granule docking and release.The Journal of cell biology · 2019Article
- In vitro fusion of single synaptic and dense core vesicles reproduces key physiological properties.Nature communications · 2019Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In pancreatic β-cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood. ATP binding cassette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion. RNAi inter-ference-induced depletion in cultured pancreatic β-cells shows that ABCG1 is needed to stabilize newly made insulin granules against lysosomal degradation; ABCA1 is also involved but to a lesser extent. Both transporters are also required for optimum glucose-stimulated insulin secretion, likely via complementary roles. Exogenous cholesterol addition rescues knockdown-induced granule loss (ABCG1) and reduced secretion (both transporters). Another cholesterol transport protein, oxysterol binding protein (OSBP), appears to act proximally as a source of endogenous cholesterol for granule formation. Its knockdown caused similar defective stability of young granules and glucose-stimulated insulin secretion, neither of which were rescued with exogenous cholesterol. Dual knockdowns of OSBP and ABC transporters support their serial function in supplying and concentrating cholesterol for granule formation. OSBP knockdown also decreased proinsulin synthesis consistent with a proximal endoplasmic reticulum defect. Thus, membrane cholesterol distribution contributes to insulin homeostasis at production, packaging, and export levels through the actions of OSBP and ABCs G1 and A1.
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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.