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.
LanguageEnglish
Pages813-815
JournalScience
Volume271
Issue number5250
Publication statusPublished - Feb 1996

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Exocytosis
Insulin-Secreting Cells
Hypoglycemic Agents
Protein Kinase C
Adenosine Triphosphate
Cell Membrane
Potassium Channels
Insulin
Calcium
Membranes
Therapeutics

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Eliasson, L., Renstrom, E., Ammala, C., Berggren, PO., Bertorello, AM., Bokvist, K., ... Rorsman, P. (1996). PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. Science, 271(5250), 813-815.
Eliasson, L ; Renstrom, E ; Ammala, C ; Berggren, PO ; Bertorello, AM ; Bokvist, K ; Chibalin, A ; Deeney, JT ; Flatt, Peter ; Gabel, J ; Gromada, J ; Larsson, O ; Lindstrom, P ; Rhodes, CJ ; Rorsman, P. / PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. In: Science. 1996 ; Vol. 271, No. 5250. pp. 813-815.
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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 (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.",
author = "L Eliasson and E Renstrom and C Ammala and PO Berggren and AM Bertorello and K Bokvist and A Chibalin and JT Deeney and Peter Flatt and J Gabel and J Gromada and O Larsson and P Lindstrom and CJ Rhodes and P Rorsman",
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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, vol. 271, no. 5250, pp. 813-815.

PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. / Eliasson, L; Renstrom, E; Ammala, C; Berggren, PO; Bertorello, AM; Bokvist, K; Chibalin, A; Deeney, JT; Flatt, Peter; Gabel, J; Gromada, J; Larsson, O; Lindstrom, P; Rhodes, CJ; Rorsman, P.

In: Science, Vol. 271, No. 5250, 02.1996, p. 813-815.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Eliasson, L

AU - Renstrom, E

AU - Ammala, C

AU - Berggren, PO

AU - Bertorello, AM

AU - Bokvist, K

AU - Chibalin, A

AU - Deeney, JT

AU - Flatt, Peter

AU - Gabel, J

AU - Gromada, J

AU - Larsson, O

AU - Lindstrom, P

AU - Rhodes, CJ

AU - Rorsman, P

PY - 1996/2

Y1 - 1996/2

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 (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.

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 (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.

M3 - Article

VL - 271

SP - 813

EP - 815

JO - Science

T2 - Science

JF - Science

SN - 0036-8075

IS - 5250

ER -

Eliasson L, Renstrom E, Ammala C, Berggren PO, Bertorello AM, Bokvist K et al. PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells. Science. 1996 Feb;271(5250):813-815.