Impaired phosphoinositide metabolism in glucose-incompetent islets
of neonatally streptozotocin-diabetic rats.
Morin, Laurent, Marie-H[acute]elene Giroix, Marie-Noelle Gangnerau,
Danielle Bailb[acute]e, and Bernard Portha.
Laboratoire de Physiopathologie de la Nutrition, URA CNRS 307,
Universit[acute]e Paris 7 (Denis Diderot), F-75251 Paris cedex 05,
France
APStracts 4:0022E, 1997.
The effects of nutrient and neurotransmitter stimuli upon insulin
release, loss of phosphoinositides (PI) and production of inositol
phosphates (InsP) were investigated in islets from neonatally
streptozotocin-injected rats (n-STZ rats). In islets from n-STZ rats,
insulin secretory responses to 16.7 mM D-glucose and 10.0 mM D
-glyceraldehyde were reduced, compared to controls. Contents in
phosphatidylinositol 4-monophosphate (PtdIns-4-P) and
phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2), but not in
phosphatidylinositol (PtdIns), were diminished. Glucose effects upon
breakdown of PtdIns-4-P and PtdIns-4,5-P2 and upon total InsP
accumulation were both reduced. D-glucose was unable to increase the
levels of both inositol trisphosphate isomers, Ins-1,3,4-P3 and Ins
-1,4,5-P3. Glyceraldehyde also failed to promote InsP formation. By
contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin
to stimulate insulin secretion and InsP generation was still
observed. Thus, a disturbed coupling between nutrient recognition and
activation of phospholipase C, possibly together with a shortage of
available polyphosphoinositides, could be responsible for the altered
islet PI turnover in the n-STZ rats. It is proposed that such defects
may contribute to the impairment of glucose-stimulated insulin
secretion in this model of non-insulin-dependent diabetes.
Received 15 May 1996; accepted in final form 30 December 1996.
APS Manuscript Number E242-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997