Rapid Ca2+ influx and diacylglycerol synthesis in growth hormone- mediated islet β-cell mitogenesis

Åke Sjöholm, Qimin Zhang, Nils Welsh, Anders Hansson, Olof Larsson, Michael Tally, Per Olof Berggren

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Growth hormone (GH) is an important mitogenic stimulus for the insulin- producing β-cell. We investigated the effects of GH on Ca2+ handling and diacylglycerol (DAG) and cAMP formation in the β-cell. GH elicited a rapid increase in the cytoplasmic free [Ca2+], which required extracellular Ca2+ and was also blocked by pertussis toxin or protein kinase C (PKC) inhibition. GH also elevated islet DAG content, which should lead to PKC activation. Pertussis toxin and PKC inhibitors obliterated the mitogenicity of GH, suggesting involvement of GTP-binding proteins. PKC activation stimulated β-cell proliferation, and it also activated phospholipase D. Islet cAMP content was not elevated by GH. Addition of a specific protein kinase A antagonist failed to influence the mitogenicity of GH, whereas a stimulatory cAMP agonist stimulated β-cell replication. We conclude that GH rapidly increases the β-cell cytoplasmic free [Ca2+] and also evokes a similar increase in DAG content via a phosphatidylcholine-specific phospholipase C, but does not affect mitogen-activated protein kinases, phospholipase D, or the cAMP signaling pathway. This rise in DAG may be of importance in translation of the stimulatory signal of GH into a proliferative response by the β-cell, which seems to occur through GTP- binding proteins and PKC-dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)21033-21040
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number28
DOIs
StatePublished - Jul 14 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sjöholm, Å., Zhang, Q., Welsh, N., Hansson, A., Larsson, O., Tally, M., & Berggren, P. O. (2000). Rapid Ca2+ influx and diacylglycerol synthesis in growth hormone- mediated islet β-cell mitogenesis. Journal of Biological Chemistry, 275(28), 21033-21040. https://doi.org/10.1074/jbc.M001212200