Abstract
Summary Background and objective: Hyperinsulinemia attributable to augmented concentrations of insulin and proinsulin in plasma increases plasma PAI-1 activity in vivo and may contribute to acceleration of atherogenesis in patients with non-insulin-dependent diabetes mellitus (NIDDM). The present study is designed to verify that the increase in PAI-1 activity is specifically attributable to insulin and proinsulin and not to an acute phase reaction possibly triggered by endotoxins. Methods and results: To simulate hyper(pro)insulinemia seen with NIDDM, equimolar concentrations of insulin (1 IU/kg, n = 17), proinsulin (n = 16), C-peptide (n = 4), and placebo (n = 16) were infused intravenously over 1 h in 53 conscious rabbits maintained euglycemic. At 3 h plasma PAI-1 activity was significantly higher with insulin (15.8 ± 1.4 AU/ml, ±SEM) and proinsulin (17.2 ± 1.5 AU/ml) than with C-peptide (7.4 ± 0.6 AU/ml) and placebo (6.2 ± 0.6 AU/ml, p Conclusions: With the exclusion of endotoxin contamination and the comparable time courses of plasma fibrinogen concentration and t-PA activity among all treatment groups, induction of PAI-1 activity in plasma can be attributed to specific action by insulin and proinsulin rather than manifestation of an acute phase reaction.
Published Version
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