Rapid Association of Protein Kinase C-ε with Insulin Granules Is Essential for Insulin Exocytosis

Carlos F. Mendez, Ingo B. Leibiger, Barbara Leibiger, Marianne Høy, Jesper Gromada, Per Olof Berggren, Alejandro M. Bertorello

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57 Scopus citations


Glucose-dependent exocytosis of insulin requires activation of protein kinase C (PKC). However, because of the great variety of isoforms and their ubiquitous distribution within the β-cell, it is difficult to predict the importance of a particular isoform and its mode of action. Previous data revealed that two PKC isoforms (a and ε) translocate to membranes in response to glucose (Zaitzev, S. V., Efendic, S., Arkhammar, P., Bertorello, A. M., and Berggren, P. O. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 9712-9716). Using confocal microscopy, we have now established that in response to glucose, PKC-ε but not PKC-α associates with insulin granules and that green fluorescent protein-tagged PKC-ε changes its distribution within the cell periphery upon stimulation of β-cells with glucose. Definite evidence of PKC-ε requirement during insulin granule exocytosis was obtained by using a dominant negative mutant of this isoform. The presence of this mutant abolished glucose-induced insulin secretion, whereas transient expression of the wildtype PKC-ε led to a significant increase in insulin exocytosis. These results suggest that association of PKC-ε with insulin granule membranes represents an important component of the secretory network because it is essential for insulin exocytosis in response to glucose.

Original languageEnglish (US)
Pages (from-to)44753-44757
Number of pages5
JournalJournal of Biological Chemistry
Issue number45
StatePublished - Nov 7 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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