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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
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Citations to this article in year 2020 (10)

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The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis
GR Carrat, E Haythorne, A Tomas, L Haataja, A Müller, P Arvan, A Piunti, K Cheng, M Huang, TJ Pullen, E Georgiadou, T Stylianides, NS Amirruddin, V Salem, W Distaso, A Cakebread, KJ Heesom, PA Lewis, DJ Hodson, LJ Briant, AC Fung, RB Sessions, F Alpy, AP Kong, PI Benke, F Torta, AK Teo, I Leclerc, M Solimena, DB Wigley, GA Rutter
Molecular Metabolism 2020
ABCA12 regulates insulin secretion from β‐cells
GM Ursino, Y Fu, DL Cottle, N Mukhamedova, LK Jones, H Low, MS Tham, WJ Gan, NA Mellett, PP Das, JM Weir, M Ditiatkovski, S Fynch, P Thorn, HE Thomas, PJ Meikle, HC Parkington, IM Smyth, D Sviridov
EMBO reports 2020
Do ABC transporters regulate plasma membrane organization?
A Wu, K Wojtowicz, S Savary, Y Hamon, T Trombik
Cellular & Molecular Biology Letters 2020
Identification of Sca-1+Abcg1+ bronchioalveolar epithelial cells as the origin of lung adenocarcinoma in Gprc5a-knockout mouse model through the interaction between lung progenitor AT2 and Lgr5 cells
H Yin, Z Jiang, X Feng, Z Ji, W Jin
Oncogene 2020
Role of High‐Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control
B Manandhar, BJ Cochran, KA Rye
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2020
Combined transcriptome and proteome profiling of the pancreatic β-cell response to palmitate unveils key pathways of β-cell lipotoxicity
M Lytrivi, K Ghaddar, M Lopes, V Rosengren, A Piron, X Yi, H Johansson, J Lehtiö, M Igoillo-Esteve, DA Cunha, L Marselli, P Marchetti, H Ortsäter, DL Eizirik, M Cnop
BMC Genomics 2020
Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns at ABCG1
Y Liu, Y Shen, T Guo, LD Parnell, KE Westerman, CE Smith, JM Ordovas, CQ Lai
Frontiers in Genetics 2020
Insulin granule biogenesis and exocytosis
M Omar-Hmeadi, O Idevall-Hagren
Cellular and Molecular Life Sciences 2020
Lung Cancer Inhibition by Betulinic Acid Nanoparticles via Adenosine 5’-Triphosphate (ATP)-Binding Cassette Transporter G1 Gene Downregulation
H Zhao, X Mu, X Zhang, Q You
Medical science monitor : international medical journal of experimental and clinical research 2020
HDL inhibits endoplasmic reticulum stress-induced apoptosis of pancreatic β-cells in vitro by activation of Smoothened
M Yalcinkaya, A Kerksiek, K Gebert, W Annema, R Sibler, S Radosavljevic, D Lütjohann, L Rohrer, A von Eckardstein
Journal of lipid research 2020

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