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Science 9 February 1996:
Vol. 271. no. 5250, pp. 813 - 815
DOI: 10.1126/science.271.5250.813
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Reports

PKC-Dependent Stimulation of Exocytosis by Sulfonylureas in Pancreatic Cells

Lena Eliasson,  Erik Renström,  Carina Ämmälä,  Per-Olof Berggren,  Alejandro M. Bertorello,  Krister Bokvist,  Alexander Chibalin,  Jude T. Deeney,  Peter R. Flatt,  Jakob Gäbel,  Jesper Gromada,  Olof Larsson,  Per Lindström,  Christopher J. Rhodes,  Patrik Rorsman (1)

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.


L. Eliasson, C. Ämmälä, J. Gäbel, Department of Physiology and Pharmacology, Division of Biophysics, University of Göteborg, Medicinaregatan 11, S-413 90 Göteborg, Sweden.
E. Renström, K. Bokvist, J. Gromada, P. Rorsman, Department of Islet Cell Physiology, Novo Nordisk A/S, Symbion Science Park, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
P.-O. Berggren, A. M. Bertorello, A. Chibalin, O. Larsson, Department of Molecular Medicine, Karolinska Institute, Rolf Luft's Center for Diabetes Research, S-171 76 Stockholm, Sweden.
J. T. Deeney, Diabetes and Metabolism Unit, Evans Department of Medicine and Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
P. R. Flatt, Department of Biological and Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.
P. Lindström, Department of Histology and Cell Biology, University of Umeå, S-901 87 Umeå, Sweden.
C. J. Rhodes, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
(1) To whom correspondence should be addressed. E-mail: PaR{at}novo.dk


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