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 Citations (Scopus)

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

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Diglycerides
Islets of Langerhans
Growth Hormone
Protein Kinase C
Phospholipase D
Pertussis Toxin
GTP-Binding Proteins
Chemical activation
Protein C Inhibitor
Cell proliferation
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
Cell Proliferation
Insulin

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

Rapid Ca2+ influx and diacylglycerol synthesis in growth hormone- mediated islet β-cell mitogenesis. / Sjöholm, Åke; Zhang, Qimin; Welsh, Nils; Hansson, Anders; Larsson, Olof; Tally, Michael; Berggren, Per Olof.

In: Journal of Biological Chemistry, Vol. 275, No. 28, 14.07.2000, p. 21033-21040.

Research output: Contribution to journalArticle

Sjöholm, Å, Zhang, Q, Welsh, N, Hansson, A, Larsson, O, Tally, M & Berggren, PO 2000, 'Rapid Ca2+ influx and diacylglycerol synthesis in growth hormone- mediated islet β-cell mitogenesis', Journal of Biological Chemistry, vol. 275, no. 28, pp. 21033-21040. https://doi.org/10.1074/jbc.M001212200
Sjöholm, Åke ; Zhang, Qimin ; Welsh, Nils ; Hansson, Anders ; Larsson, Olof ; Tally, Michael ; Berggren, Per Olof. / Rapid Ca2+ influx and diacylglycerol synthesis in growth hormone- mediated islet β-cell mitogenesis. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 28. pp. 21033-21040.
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