Insulin-like growth factor II inhibits glucose-induced insulin exocytosis

Q Zhang, PO Berggren, O Larsson, K Hall… - … and biophysical research …, 1998 - Elsevier
Q Zhang, PO Berggren, O Larsson, K Hall, M Tally
Biochemical and biophysical research communications, 1998Elsevier
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 …
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.
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