AJP - Endocrinology and Metabolism, Vol 259, Issue 1 E73-E79, Copyright © 1990 by American Physiological Society
Activation of PKC inhibits NaF-induced inositol phospholipid turnover in rat insulinoma cells
T. Yamatani, A. Yamaguchi, A. Nakamura, T. Morishita, S. Kadowaki, T. Fujita and T. Chiba
Department of Internal Medicine, Kobe University School of Medicine, Japan.
An investigation was done to elucidate the regulatory role of protein
kinase C (PKC) in insulin release and also the effects of PKC activation on
NaF-induced inositol phospholipid (PI) turnover in and insulin release from
rat insulinoma cells (RINr). NaF stimulated insulin secretion in
association with an increase in [3H]inositol phosphate formation in RINr
cells. Furthermore, NaF induced a rapid decrease in 32P-labeling of
phosphatidylinositol-4,5-diphosphate (PIP2) with a concomitant increase of
[32P]phosphatidic acid in prelabeled cells. In contrast, NaF had no effect
on cyclic AMP production. Although phorbol 12,13-dibutyrate (PDBu) also
stimulated insulin release, on concomitant administration of NaF and PDBu,
insulin secretion was clearly less than that expected on the basis of an
additive action. Moreover, PDBu significantly inhibited NaF-enhanced PI
turnover. However, this inhibition was abolished after downregulating PKC
by pretreating RINr cells with PDBu. Thus NaF-induced insulin release from
RINr cells appears to involve enhancement of PI turnover. Moreover, because
NaF is known to activate guanine nucleotide binding proteins (G proteins)
directly, PKC activation appears to induce a mechanism that inhibits
stimulus-secretion coupling at a level between G protein and phospholipase
C-induced PIP2 hydrolysis.
