Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells

American Journal of Physiology. Gastrointestinal and Liver Physiology
Matheus de Castro FonsecaM Fatima Leite

Abstract

Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes. Membrane cholesterol was depleted in vitro with metyl-β-cyclodextrin (MβCD) and in vivo with lovastatin. Insulin-induced calcium (Ca2+) signals studies were examined in HepG2 cells and in freshly isolated rat hepatocytes as well as in whole liver in vivo by intravital confocal imaging. Liver regeneration was studied by 70% partial hepatectomy (PH), and hepatocyte proliferation was assessed by PCNA staining. A subpopulation of IR was found in membrane microdomains enriched in cholesterol. Depletion of cholesterol from plasma membrane resulted in redistribution of the IR along the cells, which was associated with impaired insulin-induced nuclear Ca2+ signals, a ...Continue Reading

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Citations

Sep 28, 2018·Frontiers in Immunology·Amanda R R VicentinoMarcelo R Fantappié
Jan 1, 2020·Journal of Diabetes and Metabolic Disorders·Thai Quoc TranFuu-Jen Tsai
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Leonardo GatticchiEric C Schirmer
May 31, 2021·Biochemical Pharmacology·Miguel A LasunciónDiego Gómez-Coronado

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Methods Mentioned

BETA
confocal microscopy
protein assay
enzyme linked immunosorbent assay
Assay
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ImageJ
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