Article
Reference
Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells
AROUS, Caroline, et al.
Abstract
Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2-AKT signaling. We observed for the first time a cooperation between different AKT isoforms and focal adhesion kinase (FAK)-dependent adhesion signaling, which either controlled GSIS or prevented insulin secretion under fasting conditions. Indeed, β-cells form integrin-containing adhesions, which provide anchorage to the pancreatic extracellular matrix and are the origin of intracellular signaling via FAK and paxillin. Under low-glucose conditions, β-cells adopt a starved adhesion phenotype consisting of actin stress fibers and large peripheral focal adhesion. [...]
AROUS, Caroline, et al. Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells. Journal of Biological Chemistry, 2020, vol. 295, no. 49, p. 16510-16528
DOI : 10.1074/jbc.RA120.012957 PMID : 32934005
Available at:
http://archive-ouverte.unige.ch/unige:153888
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Integrin and autocrine IGF2-pathways control fasting insulin secretion in β-cells
Caroline Arous1, Maria Luisa Mizgier2, Katharina Rickenbach1, Michel Pinget2, Karim Bouzakri2* and Bernhard Wehrle-Haller1*
From the 1 Department of Cell Physiology and Metabolism, Centre Médical Universitaire, University of Geneva, Switzerland
2UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, France
Running title : Integrin and IGF2-pathways control fasting insulin secretion
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Supp info 1: AG1024 did not induced cell death in low glucose condition. Rat primary β- cells were cultured in 2.8 mM glucose medium for 5h, containing none (CTL) or AG1024. After cell fixation, TUNEL assay were performed according to the commercial instruction.
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Supp Info 2: Inhibition of PI3K activity induced remodeling in low glucose condition but blunted glucose-induced remodeling in MIN6B1 cell. MIN6B1 were cultured in 2.8 mM glucose for 4h in presence of LY294002 (10 µM) or not, and then stimulated or not for 20 min with 16.7 mM glucose. Cell were subsequently fixed and stained for actin (phalloidin in cyan) and paxillin (green). All images are fully representative of 3 independent experiments. Scale bar: 10µm.
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Supp info 3: Dasatinib and saracatinib effect on phospho-c-Src and adhesion remodeling.
MIN6B1 cells were cultured in 2.8 mM glucose for 3h in presence or not (CTL) of dasatinib (dasat) or saracatinib (sara) and then stimulated or not with 16.7 mM glucose for 20 min in the continued presence of the inhibitors. Cell were subsequently fixed and stained for actin (phalloidin), paxillin (green) and phospho (Y418) c-Src (red). All images are fully representative of 3 independent experiments. Scale bar: 10µm.
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Supp info 4: Effect of inhibitors on adhesion remodeling in rat primary β-cell. Rat primary β-cells were cultured in 2.8 mM glucose for 4h in presence or not (CTL) of inhibitors and then stimulated or not for 20 min with 16.7 mM glucose. PF562271 (PF56: 0.1 µM), Saracatinib (Sara:0.1 µM), ROCK inhibitor (Y27632: 50 µM), Rac1 inhibitor (Rac1: 0.2 µM) and Rho activator (RhoAc: 0.25 µg/ml). Cell were subsequently fixed and stained for actin (phalloidin) and paxillin (green). All images are fully representative of 3 independent experiments. Scale bar: 10µm.
