Low molecular weight GTP-binding proteins are altered in platelet hyperaggregation in IDDM.
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.
Bastyr
E J
EJ
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1060.
Lu
J
J
Stowe
R
R
Green
A
A
Vinik
A I
AI
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
D010738:Type C Phospholipases; D019204:GTP-Binding Proteins