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

L Eliasson, E Renstrom, C Ammala, PO Berggren, AM Bertorello, K Bokvist, A Chibalin, JT Deeney, Peter Flatt, J Gabel, J Gromada, O Larsson, P Lindstrom, CJ Rhodes, P Rorsman

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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 (K-ATP 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 K-ATP 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
Publication statusPublished - Feb 1996

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    Eliasson, L., Renstrom, E., Ammala, C., Berggren, PO., Bertorello, AM., Bokvist, K., Chibalin, A., Deeney, JT., Flatt, P., Gabel, J., Gromada, J., Larsson, O., Lindstrom, P., Rhodes, CJ., & Rorsman, P. (1996). PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. Science, 271(5250), 813-815.