title: Low molecular weight GTP-binding proteins are altered in platelet hyperaggregation in IDDM.
abstract: We examined the hypothesis that hyperaggregating platelets from patients with insulin dependent diabetes mellitus (IDDM) have an alteration in location and function of the guanine nucleotide (GTP)-binding proteins. Platelets from 10 IDDM and 12 age-matched healthy control subjects were collected and washed. Thrombin-induced platelet aggregation (0.025 and 0.05 units for 60 seconds) was increased in IDDM (8.3 +/- 1.8% vs 22.3 +/- 4.4%, P < .05 and 49.9 +/- 7.3% vs 70.9 +/- 7.0%, P < .05). Four small molecular weight GTP-binding proteins were identified by binding of [32P]-GTP on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the cytosol and membranes of these platelets. Each showed specificity for binding [32P]-GTP by competitive inhibition with unlabeled GTP. The total of the 27/28 kDa proteins was decreased in the membrane fraction (414 +/- 30 vs 252 +/- 40 dpm micrograms-1 protein x min, P < .05) and increased in the cytosolic fraction (62 +/- 8 vs 129 +/- 21 dpm unit-1 LDH x min, P < .05) in IDDM. The 21 kDa protein (60.3 +/- 3.5 vs 45.4 +/- 2.9 dpm micrograms-1 protein x min, P < .05) was decreased in platelet membrane in persons with IDDM. In conclusion, increased platelet aggregation in IDDM is accompanied by an altered cellular distribution of a 27/28 kDa GTP-binding protein. These data suggest that the low molecular weight GTP-binding proteins of the 27/28 kDa range may play an important regulatory role in the hyperaggregatory platelets in diabetes.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1060.
authors.forename: E J
authors.initials: EJ
authors.lastname: Bastyr
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Stowe
authors.forename: A
authors.initials: A
authors.lastname: Green
authors.forename: A I
authors.initials: AI
authors.lastname: Vinik
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000737:chemistry*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D008297:Male; D008970:Molecular Weight; D010974:Platelet Aggregation; D010738:Type C Phospholipases / Q000032:analysis
chemical_list: D010738:Type C Phospholipases; D019204:GTP-Binding Proteins