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

Détails

ID Serval
serval:BIB_B20D60DF864D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Postreceptor signalling of growth hormone and prolactin and their effects in the differentiated insulin-secreting cell line, INS-1
Périodique
Endocrinology
Auteur(s)
Sekine  N., Ullrich  S., Regazzi  R., Pralong  W. F., Wollheim  C. B.
ISSN
0013-7227 (Print)
Statut éditorial
Publié
Date de publication
05/1996
Volume
137
Numéro
5
Pages
1841-50
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
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 because Rp-cyclic adenosine-3', 5'-monophosphorothioate, a competitive inhibitor of protein kinase A, abolished hGH-induced [Ca2+]i rises and DNA synthesis. cAMP appears to play a permissive role, although hGH failed to raise cellular cAMP levels. These results support the idea that activation of JAK2 is a major signaling event, whereas the [CA2+]i rise is not a prerequisite, for the mitogenic effects of GH and PRL in insulin-secreting cells.
Mots-clé
Animals Calcium/metabolism Cattle Cell Line Culture Media Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors DNA/biosynthesis Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology Growth Hormone/metabolism/*pharmacology Humans Insulin/*secretion Janus Kinase 2 Phenols/pharmacology Phosphotyrosine/metabolism Prolactin/metabolism/*pharmacology Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism *Proto-Oncogene Proteins Sheep *Signal Transduction
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:30
Dernière modification de la notice
20/08/2019 16:20
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