Protein kinase Cδ plays a non-redundant role in insulin secretion in pancreatic β cells

Toyoyoshi Uchida, Noseki Iwashita, Mica Ohara-Imaizumi, Takeshi Ogihara, Shintaro Nagai, Jong Bock Choi, Yoshifumi Tamura, Norihiro Tada, Ryuzo Kawamori, Keiichi I. Nakayama, Shinya Nagamatsu, Hirotaka Watada

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Abstract

Protein kinase C (PKC) is considered to modulate glucose-stimulated insulin secretion. Pancreatic β cells express multiple isoforms of PKCs; however, the role of each isoform in glucose-stimulated insulin secretion remains controversial. In this study we investigated the role of PKCδ, a major isoform expressed in pancreatic β cells on β cell function. Here, we showed that PKCδ null mice manifested glucose intolerance with impaired insulin secretion. Insulin tolerance test showed no decrease in insulin sensitivity in PKCδ null mice. Studies using islets isolated from these mice demonstrated decreased glucose- and KCl-stimulated insulin secretion. Perifusion studies indicated that mainly the second phase of insulin secretion was decreased. On the other hand, glucose-induced influx of Ca2+ into β cells was not altered. Immunohistochemistry using total internal reflection fluorescence microscopy and electron microscopic analysis showed an increased number of insulin granules close to the plasma membrane in β cells of PKCδ null mice. Although PKC is thought to phosphorylate Munc18-1 and facilitate soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors complex formation, the phosphorylation of Munc18-1 by glucose stimulation was decreased in islets of PKCδ null mice. We conclude that PKCδ plays a non-redundant role in glucose-stimulated insulin secretion. The impaired insulin secretion in PKCδ null mice is associated with reduced phosphorylation of Munc18-1.

Original languageEnglish
Pages (from-to)2707-2716
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number4
DOIs
Publication statusPublished - Jan 26 2007

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Uchida, T., Iwashita, N., Ohara-Imaizumi, M., Ogihara, T., Nagai, S., Choi, J. B., ... Watada, H. (2007). Protein kinase Cδ plays a non-redundant role in insulin secretion in pancreatic β cells. Journal of Biological Chemistry, 282(4), 2707-2716. https://doi.org/10.1074/jbc.M610482200