title: Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat.
abstract: Decreased plasma fibrinolysis may contribute to accelerated atherothrombosis in diabetes. To observe whether hyperglycemia and hyperinsulinemia, common findings in type 2 diabetes, acutely affect plasma fibrinolysis in vivo, we evaluated plasma fibrinolysis (lysis of fibrin plates, free PAI-1 activity and t-PA activity) in the rat after a hyperglycemic euinsulinemic clamp (n=8), an euglycemic hyperinsulinemic clamp (n=7) or a saline infusion (n=15). Plasma fibrinolytic activity was sharply reduced after both the hyperglycemic and hyperinsulinemic clamps as compared to the respective controls (mean lysis areas on the fibrin plate, 139+/-21 vs. 323+/-30 mm2, p<0.001; 78+/-27 vs. 312+/-27 mm2 p<0.001, respectively). Plasma PAI-1 activity was greater after both hyperglycemic and hyperinsulinemic clamps as compared to saline infusion (6.6+/-2.6 vs. 1.6+/-0.6 IU/ml, p<0.001; 26+/-4 vs. 1.3+/-0.7 IU/ml, p<0.0001, respectively). Plasma t-PA activity was significantly reduced both after the hyperglycemic (0.36+/-0.15 vs. 2.17+/-0.18 IU/ml in controls, p<0.001) and the hyperinsulinemic (0.3+/-0.1 vs. 2.3+/-0.3 IU/ml in control, p<0.001) clamps. These data show that in vivo both acute hyperglycemia and acute hyperinsulinemia can decrease plasma fibrinolytic potential and that this is due to increased plasma PAI-1 and decreased free t-PA activities.
authors.affiliation: Department of Medicine and Aging Science, University of Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pandolfi
authors.forename: A
authors.initials: A
authors.lastname: Giaccari
authors.forename: C
authors.initials: C
authors.lastname: Cilli
authors.forename: M M
authors.initials: MM
authors.lastname: Alberta
authors.forename: L
authors.initials: L
authors.lastname: Morviducci
authors.forename: E A
authors.initials: EA
authors.lastname: De Filippis
authors.forename: A
authors.initials: A
authors.lastname: Buongiorno
authors.forename: G
authors.initials: G
authors.lastname: Pellegrini
authors.forename: F
authors.initials: F
authors.lastname: Capani
authors.forename: A
authors.initials: A
authors.lastname: Consoli
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005342:Fibrinolysis; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006943:Hyperglycemia / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D005947:Glucose