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Citations to this article

An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic β cells
Jeffrey M. Sturek, … , Raghavendra G. Mirmira, Catherine C. Hedrick
Jeffrey M. Sturek, … , Raghavendra G. Mirmira, Catherine C. Hedrick
Published June 7, 2010
Citation Information: J Clin Invest. 2010;120(7):2575-2589. https://doi.org/10.1172/JCI41280.
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Research Article Metabolism Article has an altmetric score of 1

An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic β cells

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Abstract

Cholesterol is a critical component of cell membranes, and cellular cholesterol levels and distribution are tightly regulated in mammals. Recent evidence has revealed a critical role for pancreatic β cell–specific cholesterol homeostasis in insulin secretion as well as in β cell dysfunction in diabetes and the metabolic response to thiazolidinediones (TZDs), which are antidiabetic drugs. The ATP-binding cassette transporter G1 (ABCG1) has been shown to play a role in cholesterol efflux, but its role in β cells is currently unknown. In other cell types, ABCG1 expression is downregulated in diabetes and upregulated by TZDs. Here we have demonstrated an intracellular role for ABCG1 in β cells. Loss of ABCG1 expression impaired insulin secretion both in vivo and in vitro, but it had no effect on cellular cholesterol content or efflux. Subcellular localization studies showed the bulk of ABCG1 protein to be present in insulin granules. Loss of ABCG1 led to altered granule morphology and reduced granule cholesterol levels. Administration of exogenous cholesterol restored granule morphology and cholesterol content and rescued insulin secretion in ABCG1-deficient islets. These findings suggest that ABCG1 acts primarily to regulate subcellular cholesterol distribution in mouse β cells. Furthermore, islet ABCG1 expression was reduced in diabetic mice and restored by TZDs, implicating a role for regulation of islet ABCG1 expression in diabetes pathogenesis and treatment.

Authors

Jeffrey M. Sturek, J. David Castle, Anthony P. Trace, Laura C. Page, Anna M. Castle, Carmella Evans-Molina, John S. Parks, Raghavendra G. Mirmira, Catherine C. Hedrick

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 Total
Citations: 2 8 5 3 4 10 6 2 6 6 6 8 4 8 3 2 83
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2011 (3)

Title and authors Publication Year
Islet cholesterol accumulation due to loss of ABCA1 leads to impaired exocytosis of insulin granules
JK Kruit, N Wijesekara, JE Fox, XQ Dai, LR Brunham, GJ Searle, GP Morgan, AJ Costin, R Tang, A Bhattacharjee, JD Johnson, PE Light, BJ Marsh, PE Macdonald, CB Verchere, MR Hayden
Diabetes 2011
Type 2 Diabetes Is Associated with Reduced ATP-Binding Cassette Transporter A1 Gene Expression, Protein and Function
DC Patel, C Albrecht, D Pavitt, V Paul, C Pourreyron, SP Newman, IF Godsland, J Valabhji, DG Johnston
PloS one 2011
ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter
EJ Tarling, PA Edwards
Proceedings of the National Academy of Sciences 2011

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