Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release

Haiying Cheng, Susanne G. Straub, Geoffrey W.G. Sharp

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Both neurotransmitter release and insulin secretion occur via regulated exocytosis and share a variety of similar regulatory mechanisms. It has been suggested that Src family tyrosine kinases inhibit neurotransmitter release from neuronal cells (H. Ohnishi, S. Yamamori, K. Ono, K. Aoyagi, S. Kondo, and M. Takahashi. Proc Natl Acad Sci USA 98: 10930-10935, 2001). Thus the potential role of Src family kinases in the regulation of insulin secretion was investigated in this study. Two structurally different inhibitors of Src family kinases, SU-6656 and PP2, but not the inactive compound, PP3, enhanced Ca 2+-induced insulin secretion in both rat pancreatic islets and INS-1 cells in a concentration-dependent and time-dependent manner. Furthermore, Src family kinase-mediated insulin secretion appears to be dependent on elevated intracellular Ca2+ and independent of glucose metabolism, the ATP-dependent K+ channel, adenylyl cyclase, classical PKC isoforms, extracellular signal-regulated kinase 1/2, and insulin synthesis. The sites of action for Src family kinases seem to be distal to the elevation of intracellular Ca2+ level. These results indicate that one or more Src family tyrosine kinases exert a tonic inhibitory role on Ca2+- dependent insulin secretion.

Original languageEnglish (US)
Pages (from-to)E845-E852
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Keywords

  • Rat pancreatic islets
  • Signaling
  • Src family kinase
  • β-cell

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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