We have investigated the effect of IGF-II on glucose-induced insulin release in the pancreatic β-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 Ca2+-induced insulin release from electropermeabilized pancreatic β-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 Ca2+-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 β-cell involves pertussis toxin-sensitive G proteins and is dependent on PKC activity.
|Original language||English (US)|
|Number of pages||5|
|Journal||Biochemical and biophysical research communications|
|State||Published - Feb 4 1998|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology