Activators of protein kinase C stimulate insulin secretion from the human fetal pancreas.
The human fetal pancreas, like the adult pancreas, releases insulin in response to agents that increase intracellular levels of calcium and cyclic AMP. It differs from the adult pancreas in that glucose causes either minimal or no insulin secretion from it. Whether activation of protein kinase C will cause release of insulin from this immature cell, as it does from the adult pancreas, is unknown. This was the phenomenon examined in the experiments below. Activators of protein kinase C, 1.3 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) and 25.1 microM 1-oleoyl-2-acetylglycerol, caused significant release of insulin from cultured explants of human fetal pancreas. Lower concentrations of TPA--0.65 microM or less--had no such effect. Agents that are known to inhibit protein kinase C, 100 microM 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 2 mM polymyxin B, and 1 mM dibucaine, caused abolition of the insulinogenic effect of 1.3 microM TPA. Glucose, at 2.8, 5, and 10 mM, also inhibited the positive effect of TPA. However, when the concentration of glucose was increased to 20 or 30 mM, stimulation of insulin secretion returned to levels achieved with TPA alone. These levels were significantly higher than the minimal response achieved with 20 mM glucose. Such data support the involvement of protein kinase C activation in insulin secretion from the human fetal pancreas. It is postulated that this involvement may occur physiologically.
Tuch
B E
BE
Department of Medicine, University of Sydney, New South Wales, Australia.
Palavidis
Z
Z
Turtle
J R
JR
D004789:Enzyme Activation; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000196:embryology*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate