PHOSPHOINOSITIDES IN PLATELETS OF NIDDM 85 significant differences between the platelets from group I and the control in

We have examined thrombin-induced metabolism of phosphoinositides in the platelets from fifteen NIDDM(non-insulin-dependent diabetesmellitus)patientsandfifteen healthy subjects!control) The diabetic patients were divided into two groups. One group (group I) had diabetic retinopathy (microangiopathy) and the other group (group II) had atherosclerosis of great vessels (macroangiopathy). In platelets incubated with [32P] orthophosphate for 80min, the incorporation of 32P radioactivity into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was significantly lower in the group II than in the control. The addition of thrombin induced a marked decrease in PIP2 radioactivity at 10 sec in platelets from group I compared with that from the control. These results suggest that the breakdown of polyphosphoinositides is increased in platelets from diabetic subjects with retinopathy, and also that the formation of polyphosphoinositides is decreased in the platelets from diabetic subjects with macroangiopathy. (Endocrinol Japon 38: 81-87, 1991) THE ADDITION of agonists such as thrombin to resting human platelets initiates the processes of intracellular Ca' mobilization, secretion, fibrinogen receptor exposure, and aggregation that are the features of normal platelet function. Several laboratories have suggested that phospholipid-derived messenger molecules are important participants in these events. Thrombin causes hydrolysis of phosphatidylinositol 4,5bisphosphate (PIP2) by phospholipase C with a concomitant formation of diacylglycerol and inositol 1,4,5-trisphosphate (IP3) [1-5] and activates A2-type phospholipase to release arachidonic acid. IP3 induces the rapid discharge of Ca' from the dense tubular system [5]. Diacylglycerol is known to activate protein kinase C [6, 7]. Arachidonic acid is oxygenated to produce thromboxane A2. On the other hand, diacylglycerol is effectively phosphorylated to phosphatidic acid (PA) [8], which can then be redirected to phosphatidylinositol (PI) through CDP-diacylglycerol. PI is phosphorylated to phosphatidylinositol 4-monophosphate (PIP) and PIP2 by PI kinase and PIP kinase, respectively [9]. Platelet responsiveness to aggregating agents has been shown to be increased in both man and animals with diabetes mellitus [10, 11]. On the other hand, the alteration of platelet aggregation and arachidonic acid metabolism, as well as endothelial functions such as von Willebrand factor activity, prostacyclin release and fibrinolytic activity, and elevated low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) cholesterol levels in uncontrolled diabetes mellitus [11], participate in the pathogenesis of accelerated atherosclerosis complicated with diabetes mellitus as mnacroangiopathy. Platelet Received: July 24, 1990 Accepted: January 24, 1991 Correspondence to: Dr. Tatsuo ISHIZUKA, The Third Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan.