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

22 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

src-Family Kinases
Insulin
Neurotransmitter Agents
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Exocytosis
Islets of Langerhans
Adenylyl Cyclases
Metabolism
Rats
Protein Isoforms
Adenosine Triphosphate
Glucose

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release. / Cheng, Haiying; Straub, Susanne G.; Sharp, Geoffrey W G.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 292, No. 3, 03.2007.

Research output: Contribution to journalArticle

@article{e81b1acc63294e43afa00dc820183fbc,
title = "Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release",
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.",
keywords = "β-cell, Rat pancreatic islets, Signaling, Src family kinase",
author = "Haiying Cheng and Straub, {Susanne G.} and Sharp, {Geoffrey W G}",
year = "2007",
month = "3",
doi = "10.1152/ajpendo.00103.2006",
language = "English (US)",
volume = "292",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release

AU - Cheng, Haiying

AU - Straub, Susanne G.

AU - Sharp, Geoffrey W G

PY - 2007/3

Y1 - 2007/3

N2 - 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.

AB - 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.

KW - β-cell

KW - Rat pancreatic islets

KW - Signaling

KW - Src family kinase

UR - http://www.scopus.com/inward/record.url?scp=33947167236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947167236&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00103.2006

DO - 10.1152/ajpendo.00103.2006

M3 - Article

C2 - 17122086

AN - SCOPUS:33947167236

VL - 292

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3

ER -