PLATELET PHOSPHOINOSITIDE TURNOVER IN STREPTOZOTOCIN-INDUCED DIABETES

Increased platelet aggregation and secretion in response to various ag onists has been described in both diabetic humans and animals. Alterat ions in the platelet membrane fatty acid composition of phospholipids and changes in the prostacyclin and thromboxane formation could only p artly explain the altered platelet function in diabetes. In the presen t study, we have examined the role of phosphoinositide turnover in the diabetic platelet function. We report alterations in 2-[H-3] myo-inos itol uptake, phosphoinositide turnover, inositol phosphate and diacylg lycerol (DAG) formation, phosphoinositide mass, and phospholipase C ac tivity in platelets obtained from streptozotocin (STZ)-induced diabeti c rats. There was a significant increase in the 2-[H-3) myo-inositol u ptake in washed platelets from diabetic rats. Basal incorporation of 2 -[H-3] myoinositol into phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) or phosphatidylinositol (PI) in platelets obtained from diabetic rats was, however, not affected. Thr ombin stimulation of platelets from diabetic rats induced an increase in the hydrolysis of [P-32]PIP2 but indicated no change in the hydroly sis of [P-32]PIP and [P-32]PI as compared to their basal levels. Throm bin-induced formation of [H-3]inositol phosphates was significantly in creased in both diabetic as well as in control platelets as compared t o their basal levels. This formation of ra]inositol phosphates in diab etic platelets was greater than controls at all time intervals studied . Similarly, there was an increase in the release of DAG after thrombi n stimulation in the diabetic platelets. Based on these results, we co nclude that there is an increase in the transport of myoinositol acros s the diabetic platelet membrane and this feature, along with alterati ons in the hydrolysis of PIP2, inositol phosphates and DAG in the diab etic platelets, may play a role in increased phosphoinositide turnover which could explain the altered platelet function in STZ-induced diab etes.