Platelet phosphoinositide turnover in streptozotocin-induced diabetes.
Increased platelet aggregation and secretion in response to various agonists has been described in both diabetic humans and animals. Alterations in the platelet membrane fatty acid composition of phospholipids and changes in the prostacyclin and thromboxane formation could only partly explain the altered platelet function in diabetes. In the present study, we have examined the role of phosphoinositide turnover in the diabetic platelet function. We report alterations in 2-[3H] myo-inositol uptake, phosphoinositide turnover, inositol phosphate and diacylglycerol (DAG) formation, phosphoinositide mass, and phospholipase C activity in platelets obtained from streptozotocin (STZ)-induced diabetic rats. There was a significant increase in the 2-[3H] myo-inositol uptake in washed platelets from diabetic rats. Basal incorporation of 2-[3H] myo-inositol into phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) or phosphatidylinositol (PI) in platelets obtained from diabetic rats was, however, not affected. Thrombin stimulation of platelets from diabetic rats induced an increase in the hydrolysis of [32P]PIP2 but indicated no change in the hydrolysis of [32P]PIP and [32P]PI as compared to their basal levels. Thrombin-induced formation of [3H]inositol phosphates was significantly increased in both diabetic as well as in control platelets as compared to their basal levels. This formation of [3H]inositol phosphates in diabetic platelets was greater than controls at all time intervals studied. Similarly, there was an increase in the release of DAG after thrombin stimulation in the diabetic platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Jethmalani
S M
SM
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.
Dang
A Q
AQ
Faas
F H
FH
D000818:Animals; D001692:Biological Transport; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004075:Diglycerides / Q000097:blood; D007294:Inositol / Q000097:blood; D007295:Inositol Phosphates / Q000097:blood; D008297:Male; D008563:Membrane Lipids / Q000097:blood*; D019269:Phosphatidylinositol 4,5-Diphosphate; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D018129:Phosphatidylinositol Phosphates / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood*; D010727:Phosphoric Diester Hydrolases / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013917:Thrombin / Q000494:pharmacology
D004075:Diglycerides; D007295:Inositol Phosphates; D008563:Membrane Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D007294:Inositol; D013311:Streptozocin; D010727:Phosphoric Diester Hydrolases; D013917:Thrombin; D043265:Phosphatidylinositol Diacylglycerol-Lyase