Reduced guanine nucleotide-stimulated polyphosphoinositide specific phospholipase C in platelet hyperaggregation in IDDM.
Platelet activity is increased in persons with insulin dependent diabetes mellitus (IDDM). Receptor-medicated phospholipase C (PLC) activation and hydrolysis of phosphatidylinositol bisphosphate (PIP2) accompanies platelet activation. Previous work from our laboratory has shown that PIP2 hydrolysis is decreased in platelets of persons with IDDM. PIP2 hydrolysis is mediated via a phosphoinositide(PI)-specific PLC. PI-PLC activity is regulated by guanine nucleotide(GTP)-binding proteins. We therefore examined the hypothesis that platelet aggregations and PI turnover in platelet from subjects with IDDM is linked to alterations in PI-specific PLC activity. We found thrombin induced platelet aggregation was increased in the IDDM group. Basal PI and PIP2-specific PLC activity was not statistically different for the two groups. Guanine-nucleotide stimulated PIP2-specific PLC activity was decreased in the IDDM platelets. The mechanism for the reduced PLC activity and its role in the platelet hyperaggregation requires further study.
Bastyr
E J
EJ
Department of Internal Medicine, University of Texas Medical Branch-Galveston 77550.
Vinik
A I
AI
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D010084:Oxidation-Reduction; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000097:blood*
D006150:Guanine Nucleotides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010738:Type C Phospholipases