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

doi:10.1126/science.271.5250.813

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

Diabetes - Islet Patophysiology

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	813-815
Journal	Science
Volume	271
Issue number	5250
DOIs	https://doi.org/10.1126/science.271.5250.813
Publication status	Published - 1996

Subject classification (UKÄ)

Endocrinology and Diabetes

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10.1126/science.271.5250.813

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Eliasson, L., Renström, E., Ammala, C., Berggren, P-O., Bertorello, A. M., Bokvist, K., Chibalin, A., Deeney, J. T., Flatt, P. R., Gabel, J., Gromada, J., Larsson, O., Lindstrom, P., Rhodes, C. J., & Rorsman, P. (1996). PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. Science, 271(5250), 813-815. https://doi.org/10.1126/science.271.5250.813

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title = "PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells",

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.",

author = "Lena Eliasson and Erik Renstr{\"o}m and Carina Ammala and Per-Olof Berggren and Bertorello, {Alejandro M.} and Krister Bokvist and Alexander Chibalin and Deeney, {Jude T.} and Flatt, {Peter R.} and Jakob Gabel and Jesper Gromada and Olof Larsson and Per Lindstrom and Rhodes, {Christopher J.} and Patrik Rorsman",

year = "1996",

doi = "10.1126/science.271.5250.813",

language = "English",

volume = "271",

pages = "813--815",

journal = "Science (New York, N.Y.)",

issn = "1095-9203",

publisher = "American Association for the Advancement of Science (AAAS)",

number = "5250",

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TY - JOUR

T1 - PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells

AU - Eliasson, Lena

AU - Renström, Erik

AU - Ammala, Carina

AU - Berggren, Per-Olof

AU - Bertorello, Alejandro M.

AU - Bokvist, Krister

AU - Chibalin, Alexander

AU - Deeney, Jude T.

AU - Flatt, Peter R.

AU - Gabel, Jakob

AU - Gromada, Jesper

AU - Larsson, Olof

AU - Lindstrom, Per

AU - Rhodes, Christopher J.

AU - Rorsman, Patrik

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

U2 - 10.1126/science.271.5250.813

DO - 10.1126/science.271.5250.813

M3 - Article

VL - 271

SP - 813

EP - 815

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

SN - 1095-9203

IS - 5250

ER -

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

Abstract

Subject classification (UKÄ)

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