Insulin-like Growth Factor II Inhibits Glucose-Induced Insulin Exocytosis
Copyright policy )Insulin-like Growth Factor II Inhibits Glucose-Induced Insulin Exocytosis
We have investigated the effect of IGF-II on glucose-induced insulin release in the pancreatic beta-cell. Introduction of IGF-II during perifusion of the cells with 20 mM glucose abolished glucose-induced insulin release. Concomitant addition of IGF-II with 20 mM glucose caused a complete inhibition of insulin release. In addition, IGF-II inhibited Ca(2+)-induced insulin release from electropermeabilized pancreatic beta-cells. IGF-II had no effect on K(+)-or tolbutamide-induced insulin release. However, IGF-II could suppress K(+)-stimulated insulin release when cells were pretreated with the protein phosphatase inhibitor okadaic acid. The inhibitory effect of IGF-II on insulin release was not associated with significant changes in membrane potential, activity of the voltage-gated L-type Ca(2+)-channel or cytoplasmic free Ca2+ concentration. Pretreatment of the cells with pertussis toxin or the phorbol ester TPA abolished the inhibitory action of IGF-II on insulin release. Hence, the molecular mechanism whereby activation of the IGF-II/M6P receptor by IGF-II inhibits glucose-stimulated insulin exocytosis in the pancreatic beta-cell involves pertussis toxin-sensitive G proteins and is dependent on PKC activity.
- Karolinska Institute Sweden
- Karolinska University Hospital Sweden
Tolbutamide, Mice, Obese, In Vitro Techniques, Exocytosis, Receptor, IGF Type 2, Islets of Langerhans, Mice, Glucose, Pertussis Toxin, GTP-Binding Proteins, Insulin-Like Growth Factor II, Insulin Secretion, Okadaic Acid, Phosphoprotein Phosphatases, Potassium, Animals, Insulin, Calcium, Calcium Channels, Enzyme Inhibitors
Tolbutamide, Mice, Obese, In Vitro Techniques, Exocytosis, Receptor, IGF Type 2, Islets of Langerhans, Mice, Glucose, Pertussis Toxin, GTP-Binding Proteins, Insulin-Like Growth Factor II, Insulin Secretion, Okadaic Acid, Phosphoprotein Phosphatases, Potassium, Animals, Insulin, Calcium, Calcium Channels, Enzyme Inhibitors
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