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Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen

A Pandolfi1, A Giaccari, C Cilli

  • 1Department of Medicine and Aging Science, University of Chieti, Italy.

Acta Diabetologica
|January 5, 2002
PubMed
Summary

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Acute hyperglycemia and hyperinsulinemia in type 2 diabetes significantly reduce plasma fibrinolysis. This decrease is linked to elevated plasminogen activator inhibitor-1 (PAI-1) and reduced tissue plasminogen activator (t-PA) activity.

Area of Science:

  • Endocrinology
  • Cardiovascular Biology
  • Thrombosis Research

Background:

  • Decreased plasma fibrinolysis is implicated in the accelerated atherothrombosis observed in diabetes.
  • Hyperglycemia and hyperinsulinemia are common metabolic derangements in type 2 diabetes.

Purpose of the Study:

  • To investigate the acute in vivo effects of hyperglycemia and hyperinsulinemia on plasma fibrinolysis in rats.
  • To determine if these metabolic states impact key fibrinolytic markers.

Main Methods:

  • Utilized hyperglycemic euinsulinemic and euglycemic hyperinsulinemic clamp techniques in rats.
  • Assessed plasma fibrinolysis through fibrin plate lysis, plasminogen activator inhibitor-1 (PAI-1) activity, and tissue plasminogen activator (t-PA) activity measurements.

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Main Results:

  • Both hyperglycemic and hyperinsulinemic clamps significantly reduced plasma fibrinolytic activity compared to saline controls.
  • PAI-1 activity increased markedly following both clamp procedures.
  • Free t-PA activity was substantially diminished after both hyperglycemic and hyperinsulinemic clamps.

Conclusions:

  • Acute hyperglycemia and acute hyperinsulinemia independently decrease the plasma fibrinolytic potential in vivo.
  • These effects are mediated by increased plasma PAI-1 activity and decreased free t-PA activity.
  • Findings highlight a potential mechanism contributing to the pro-thrombotic state in diabetes.