PMID: 11932207Apr 5, 2002Paper

Hepatocyte growth factor stimulates proliferation of pancreatic beta-cells particularly in the presence of subphysiological glucose concentrations

Journal of Molecular Endocrinology
S GahrS R Hügl

Abstract

We investigated the role of hepatocyte growth factor (HGF) in beta-cell growth and its complex intracellular signal transduction pathways. Cell proliferation was measured in the beta-cell line INS-1 using [3H]thymidine incorporation. Activation of mitogenic signaling proteins was assessed using co-immunoprecipitation, immunoblot analysis and specific protein activity inhibitors in proliferation assays. HGF (1 x 375 nM) increased INS-1 cell proliferation in the presence of 3-24 mM glucose up to 45-fold vs unstimulated controls. HGF exceeded the effect of glucose alone (2 x 2-fold at 3 mM glucose and 1 x 7-fold in the presence of 15 mM glucose). The HGF-induced INS-1 cell proliferation was further increased by addition of IGF-I or GH. Stimulation with HGF activated the JAK-2/STAT-5 pathway with a subsequent activation of phosphatidylinositol-3'-kinase (PI3'K). PI3'K activation was necessary for HGF- and glucose-stimulated INS-1 cell proliferation. The effect of PI3'K was mediated via 70 kDa S6 kinase and protein kinase B, which showed maximum activation in the presence of 3-6 mM glucose. Protein kinase C was essential for HGF-induced INS-1 cell proliferation. The HGF effect was also mediated at low glucose concentrations via insu...Continue Reading

Citations

Aug 22, 2007·Cell Biochemistry and Biophysics·Nathalie Fiaschi-TaeschAdolfo Garcia-Ocaña
Sep 3, 2003·Biochemical and Biophysical Research Communications·Jun-ichi OkanoYoshikazu Murawaki
Jan 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hassan MziautMichele Solimena
Aug 17, 2011·Diabetes Management·Sara ErnstAdolfo Garcia-Ocaña
Apr 23, 2004·Expert Opinion on Biological Therapy·Poornima RaoAdolfo Garcia-Ocaña
Sep 24, 2015·Differentiation; Research in Biological Diversity·So-Yeon KimJoo-Won Park
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