Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic β cells

Carina Ämmälä, Lena Eliasson, Krister Bokvist, Per Olof Berggren, Richard E. Honkanen, Åke Sjöholm, Patrik Rorsman

Research output: Contribution to journalArticle

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Abstract

The mechanisms that regulate insulin secretion were investigated using capacitance measurements of exocytosis in single β cells maintained in tissue culture. Exocytosis was stimulated by voltage-clamp depolarizations to activate the voltage-dependent Ca2+ channels that mediate Ca2+ influx into the β cell. Under basal conditions, the exocytotic responses were small despite large Ca2+ currents. The exocytotic responses were dramatically increased (10- to 20-fold) by conditions that promote protein phosphorylation, such as activation of protein kinases A and C or inhibition of protein phosphatases. The stimulation of secretion was not due to an enhancement of Ca2+ influx and both peak and integrated Ca2+ currents were largely unaffected. Our data indicate that exocytosis in the insulin- secreting pancreatic β cell is determined by a balance between protein phosphorylation and dephosphorylation. They further suggest that although Ca2+ is required for the initiation of exocytosis, modulation of exocytosis by protein kinases and phosphatases, at a step distal to the elevation of Ca2+, is of much greater quantitative importance. Thus an elevation of Ca2+ may represent a permissive rather than a decisive factor in the regulation of the insulin secretory process.

Original languageEnglish
Pages (from-to)4343-4347
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number10
StatePublished - May 10 1994
Externally publishedYes

Fingerprint

Phosphoprotein Phosphatases
Exocytosis
Protein Kinases
Phosphorylation
Insulin
Secretory Pathway
Insulin-Secreting Cells
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Proteins

Keywords

  • Ca
  • insulin
  • membrane capacitance
  • pancreas
  • secretion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic β cells. / Ämmälä, Carina; Eliasson, Lena; Bokvist, Krister; Berggren, Per Olof; Honkanen, Richard E.; Sjöholm, Åke; Rorsman, Patrik.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 10, 10.05.1994, p. 4343-4347.

Research output: Contribution to journalArticle

Ämmälä, Carina ; Eliasson, Lena ; Bokvist, Krister ; Berggren, Per Olof ; Honkanen, Richard E. ; Sjöholm, Åke ; Rorsman, Patrik. / Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic β cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 10. pp. 4343-4347.
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