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GH signalling in pancreatic beta-cells

Sekine, N
Fujita, T
Published in Endocrine journal. 1998, vol. 45 Suppl, p. S33-40
Abstract GH and its related peptide PRL are known to stimulate proliferation and insulin biosynthesis in pancreatic beta-cells, and assumed to be involved in their functional maturation. We investigated signal transduction of GH and PRL in insulin-secreting cells using the differentiated rat insulinoma cell line, INS-1. In these cells, both hormones stimulated proliferation and DNA synthesis, increased viability, cellular metabolism and insulin content. GH induced cytosolic Ca2+ ([Ca2+]i) rises, which appear to be due to Ca2+-influx through voltage-gated Ca2+-channels. GH also promoted tyrosine phosphorylation of several proteins in INS-1 cells, one of which was identified as JAK2 tyrosine kinase. Moreover, GH caused changes in DNA binding of nuclear proteins to some interferon-gamma-activated sites. Verapamil inhibited neither DNA synthesis nor JAK2 phosphorylation stimulated by GH, whereas a tyrosine kinase inhibitor, lavendustin A, blocked the mitogenic effect. Involvement of cAMP is also suggested because Rp-cAMPS, a competitive inhibitor of protein kinase A, abolished both [Ca2+]i rises and DNA synthesis stimulated by GH. The effects of GH and PRL on [Ca2+]i, JAK2 phosphorylation and DNA binding of the STATs were virtually identical in INS-1 cells. Since both hormones failed to activate MAP kinase in these cells, it is strongly suggested that activation of the JAK-STAT pathway is the major signalling event for the mitogenic effects of GH and PRL in beta-cells. It remains to be clarified whether the [Ca2+]i rise mediates other effects of these hormones.
Keywords Calcium/metabolismCells, CulturedEnzyme ActivationHuman Growth Hormone/pharmacology/physiologyHumansInsulin/secretionIslets of Langerhans/drug effects/physiology/secretionProlactin/pharmacologyProtein-Tyrosine Kinases/metabolismSignal Transduction/physiologyTranscriptional Activation
PMID: 9790227
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SEKINE, N, WOLLHEIM, Claes, FUJITA, T. GH signalling in pancreatic beta-cells. In: Endocrine journal, 1998, vol. 45 Suppl, p. S33-40. https://archive-ouverte.unige.ch/unige:35087

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Deposited on : 2014-03-28

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