DECREASED ATP-INDUCED SYNTHESIS AND CA2-STIMULATED DEGRADATION OF POLYPHOSPHOINOSITIDES IN PANCREATIC-ISLETS FROM NEONATALLY STREPTOZOTOCIN-DIABETIC RATS()

Phosphoinositide (PI) synthesis and hydrolysis were investigated in pa ncreatic islet homogenates from neonatal streptozotocin diabetic (n-ST Z) and control rats. In the diabetics, ATP, in absence of Ca2+ failed to increase the amount of phosphatidylinositol 4-phosphate (PtdInsP) a nd phosphatidyl inositol 4,5-bisphosphate (PtdInsP(2)) at variance wit h the pattern in controls. Also, the Ca2+-stimulated generation of ino sitol phosphates (InsP) was dramaticaly decreased, whether in the abse nce or presence of ATP. Moreover, phosphatidylinositol (PtdIns) kinase activity was reduced while PtdInsP kinase activity was not impaired. These data suggest that the suppressed formation of PtdInsP and subseq uent PtdInsP, synthesis, concomitantly with a decreased Ca2+-stimulate d phospholipase C activity, may participate to the alteration of the P I pathway, the limitation of the InsP production, and finally the impa irment of the insulin release in the n-STZ model of non-insulin-depend ent diabetes. (C) 1996 Academic Press, Inc.