PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells

Lena Eliasson, Erik Renström, Carina Ammala, Per-Olof Berggren, Alejandro M. Bertorello, Krister Bokvist, Alexander Chibalin, Jude T. Deeney, Peter R. Flatt, Jakob Gabel, Jesper Gromada, Olof Larsson, Per Lindstrom, Christopher J. Rhodes, Patrik Rorsman

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics.
Original languageEnglish
Pages (from-to)813-815
JournalScience
Volume271
Issue number5250
DOIs
Publication statusPublished - 1996

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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