AJP - Endocrinology and Metabolism, Vol 272, Issue 5 E737-E745, Copyright © 1997 by American Physiological Society
Impaired phosphoinositide metabolism in glucose-incompetent islets of neonatally streptozotocin-diabetic rats
L. Morin, M. H. Giroix, M. N. Gangnerau, D. Bailbe and B. Portha
Laboratoire de Physiopathologie de la Nutrition, Universite Paris, France.
The effects of nutrient and neurotransmitter stimuli on insulin release,
loss of phosphoinositides (PI), and production of inositol phosphates
(InsP) were investigated in islets from neonatally streptozotocin-injected
(nSTZ) rats. In islets from nSTZ rats, insulin secretory responses to 16.7
mM D-glucose and 10.0 mM D-glyceraldehyde were reduced compared with
controls. Contents in phosphatidylinositol 4-monophosphate [PtdIns(4)P] and
phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but not in
phosphatidylinositol, were diminished. Glucose effects on breakdown of
PtdIns(4)P and PtdIns(4,5)P2 and on 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 nSTZ 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 mellitus.
