Insulin-like growth factor-I-induced DNA synthesis in insulin-secreting cell line RINm5F is associated with phosphorylation of the insulin-like growth factor-I receptor and the insulin receptor substrate-2

Q. Zhang, P. O. Berggren, A. Hansson, M. Tally

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

A proliferative effect of insulin-like growth factor-I (IGF-I) was previously shown in pancreatic islets. However, the mechanism under which IGF-I actions are exerted in insulin-secreting cells is not clear. The rat insulinoma cell line, RINm5F, was shown to have both IGF-I receptors and IGF- II/mannose-6-phosphate receptors. IGF-I binding to cell surface receptors stimulated phosphorylation of 97 kDa and 93 kDa subunits of the IGF-I receptor and incorporation of [3H]thymidine into RINm5F cells. Both the IGF- I-induced protein phosphorylation and [3H]thymidine incorporation were abolished in the presence of the tyrosine kinase inhibitor, genistein. Under basal conditions, IGF-I did not induce insulin release or changes in cytosolic free Ca2+ concentration. Immunoprecipitation of proteins from RINm5F cells, using phosphotyrosine antibodies, followed by western blotting using antibody against IRS-1 revealed no distinct band of phosphorylated insulin receptor substrate (IRS)-1. Instead, tyrosine-phosphorylated IRS-2 was detected and stimulated by IGF-I when western blotting was performed using antibody against IRS-2. These results indicate that IRS-1 is not likely to be involved in IGF-I signalling in RINm5F cells. Hence, IGF-I stimulated DNA synthesis in RINm5F cells was associated with phosphorylation of IGF-I receptors and IRS-2.

Original languageEnglish (US)
Pages (from-to)573-581
Number of pages9
JournalJournal of Endocrinology
Volume156
Issue number3
DOIs
StatePublished - Mar 1 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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