Effects of low-concentration polymyxin B on insulin secretion induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), glucose, or tolbutamide from the isolated perfused rat pancreas.
To evaluate the role of protein kinase C on insulin secretion, we investigated the effects of low-concentration polymyxin B (100 mumol/L) on insulin secretion from the isolated perfused rat pancreas induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 10 nmol/L), a protein kinase C activator, glucose (10 mmol/L), or tolbutamide (738 mumol/L). Polymyxin B, a potent and relatively selective protein kinase C inhibitor at this low concentration, did significantly inhibit the gradual rise of insulin secretion induced by TPA (P less than .05). As for glucose or tolbutamide stimulation, polymyxin B significantly inhibited not only the second phase but also the first phase of insulin secretion (P less than .05) without changing the secretion patterns. Although the possibility of nonspecific effects of polymyxin B other than protein kinase C inhibition could not be excluded, the data suggest that protein kinase C might be involved in insulin secretion as a potentiating modulator.
Maki
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nunoi
K
K
Kikuchi
M
M
Fujishima
M
M
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011112:Polymyxin B / Q000008:administration & dosage / Q000494:pharmacology*; D011113:Polymyxins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology*
D007328:Insulin; D011113:Polymyxins; D014044:Tolbutamide; D011493:Protein Kinase C; D005947:Glucose; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate