GH Signalling in Pancreatic β-Cells

Endocrine Journal

TOSHIRO FUJITA²  CLAES B. WOLLHEIM¹  NOBUO SEKINE² 

[1] Division de Biochimie Clinique, Centre Médical Universitare, Département de Médecine, University of Geneva;Fourth Department of Internal Medicine, University of Tokyo School of Medicine

关键词: GH;    Pancreatic β-cells;    Cytosolic Ca2+;    Tyrosine phosphorylation;    The JAK-STAT pathway;   

DOI  :  10.1507/endocrj.45.Suppl_S33

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(36)Cited-By(12)GH and its related peptide PRL are known to stimulate proliferation and insulin biosynthesis in pancreatic β-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-γ-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 β-cells. It remains to be clarified whether the [Ca2+]i rise mediates other effects of these hormones.

【 授权许可】

Unknown