Glucose-induced phosphoinositide hydrolysis: a requirement for gtp
in calcium-induced phospholipase c activation in pancreatic
islets.
Vadakekalam, Jacob, Mary E. Rabaglia, Qing-Hui Chen, and Stewart A.
Metz.
Department of Medicine and Section of Endocrinology, University of
Wisconsin and William S. Middleton Veteran's Administration Hospital,
Madison, WI 53792
APStracts 3:0034E, 1996.
We have previously demonstrated a permissive role for GTP in insulin
secretion; in the current studies, we examined the effect of GTP on
phospholipase C (PLC) activation to explore one possible mechanism
for that observation. In rat islets pre-exposed to the GTP synthesis
inhibitors mycophenolic acid (MPA) or mizoribine (MZ), PLC activation
induced by 16.7 mM glucose (or by 20 mM [alpha]-ketoisocaproic acid)
was inhibited 63% without altering the labeling of phosphoinositide
substrates. Provision of guanine, which normalizes islet GTP content
and insulin release, prevented the inhibition of PLC by MPA. Glucose
-induced phosphoinositide hydrolysis was blocked by removal of
extracellular Ca2+ or by diazoxide. PLC induced directly by Ca2+
influx (i.e., 40 mM K+) was reduced 42% in MPA pre-treated islets but
without inhibition of the concomitant insulin release. These data
indicate that glucose-induced PLC activation largely reflects Ca2+
entry and demonstrate (for the first time in intact cells) that
adequate GTP is necessary for glucose-(and Ca2+-) induced PLC
activation, but not for maximal Ca2+-induced exocytosis.
Received 28 August 1995; accepted in final form 29 January 1996.
APS Manuscript Number E419-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96