PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells.
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.
Eliasson
L
L
Department of Physiology and Pharmacology, University of Göteborg, Sweden.
Renström
E
E
Ammälä
C
C
Berggren
P O
PO
Bertorello
A M
AM
Bokvist
K
K
Chibalin
A
A
Deeney
J T
JT
Flatt
P R
PR
Gäbel
J
J
Gromada
J
J
Larsson
O
O
Lindström
P
P
Rhodes
C J
CJ
Rorsman
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D004553:Electric Conductivity; D005089:Exocytosis / Q000187:drug effects*; D005913:Glipizide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D014044:Tolbutamide; D011493:Protein Kinase C; D005905:Glyburide; D002118:Calcium; D005913:Glipizide