Postreceptor signalling of growth hormone and prolactin and their effects in the differentiated insulin-secreting cell line, INS-1

Endocrinology
N SekineC B Wollheim

Abstract

Signal transduction of two mitogens for pancreatic beta-cells, GH and PRL, was investigated using the differentiated insulin-secreting cell line, INS-1. Addition of human GH (hGH) or ovine PRL in a serum-substitute medium increased growth, insulin content, and nutrient metabolism evaluated by tetrazolium salt reduction. hGH, bovine GH (bGH), and PRL also stimulated [3H]thymidine incorporation in a dose-dependent manner (1 pM - 1 nM). hGH induced cytosolic Ca2+ ([Ca2+]i) rises, which were transient, dependent on the presence of extracellular Ca2+, blocked by verapamil, calciseptine, and the hyperpolarizing agent diazoxide, suggesting that hGH stimulates Ca(2+)-influx through L-type Ca(2+)-channels. Similar effects on [Ca2+]i were observed with bGH or PRL. hGH caused membrane depolarization in a small proportion of the cells ( < 25%) as detected by cell-attached patch-clamp analysis. However, hGH failed to stimulate acute insulin secretion. hGH, bGH, and PRL promoted tyrosine phosphorylation of JAK2 tyrosine kinase. Verapamil inhibited neither [3H]thymidine incorporation nor JAK2 phosphorylation stimulated by hGH, whereas a tyrosine kinase inhibitor, lavendustin A, blocked the mitogenic effect. Involvement of cAMP is suggested be...Continue Reading

Citations

Feb 24, 2010·The Journal of Membrane Biology·Malika FaouziHalima Ouadid-Ahidouch
Sep 16, 2000·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·M J Thomas
Feb 18, 1999·Journal of Cellular Biochemistry·M M KauP S Wang
Aug 4, 1998·The American Journal of Physiology·S GaurH M Goodman
Apr 5, 2000·The Journal of Biological Chemistry·A SjöholmP O Berggren
Feb 26, 1999·Biochemical Pharmacology·D JanjicC B Wolheim

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