Possible involvement of diacylglycerol-activated, Ca2+-dependent protein kinase in glucose memory of the rat pancreatic B-cell.
Exposure to high concentrations of glucose potentiates insulin release from the pancreatic B-cell stimulated by various secretagogues after an interval under basal condition. We studied the role of diacylglycerol-activated, Ca2+-dependent protein kinase (protein kinase C) in this priming effect of glucose in rat pancreatic islets, using 12-O-tetradecanoyl phorbol-13-acetate (TPA), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7),N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004) and forskolin. The priming effect of glucose was mimicked by 10 nmol/l of TPA, an activator of protein kinase C, but not by 5 mumol/l of forskolin, which increases cAMP via activating adenylate cyclase. When pancreatic islets were exposed to glucose (10 mmol/l) together with 50 mumol/l of H-7, an inhibitor of protein kinase C, the secretory response to glucose (10 mmol/l) after a 30-min interval was significantly reduced compared with that in the islets previously exposed to 10 mmol/l glucose alone. In contrast, this was not the case for HA-1004, its inhibitory activity against protein kinase C being less potent than H-7. These findings suggest that protein kinase C may play an important role in the priming effect of glucose on the pancreatic B-cell.
Niki
I
I
Third Department of Internal Medicine, University of Nagoya School of Medicine, Japan.
Tamagawa
T
T
Niki
H
H
Niki
A
A
Koide
T
T
Sakamoto
N
N
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D005576:Colforsin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate