Plasminogen activator inhibitor-1 antigen concentrations during insulin and oral glucose tolerance tests in obese man

Abstract

In vitro studies have shown that insulin increases plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in cells of hepatic origin. However, in vivo studies have failed to demonstrate an acute or chronic effect of insulin infusions on PAI-1 concentrations in man. To investigate the effects of exogenous insulin infusion compared to endogenous insulin secretion, 8 obese subjects underwent an insulin tolerance test (ITT) and an oral glucose tolerance test (OGTT). During ITT, insulin levels rose from (median, range) 8 (5–18) μU ml −1 at time 0 to 140 (40–500) μU ml −1 after 30 min before falling to 12.5 (6–32) μU ml −1 at 90 min. Plasma glucose fell from 3.9 (3.1–4.7mmol −1 at time 0 to 1.8 (1.1–2.6)mmol 1 −1 after 30min. During OGTT plasma insulin rose from 6·5 (5–26) μU ml −1 at time 0 to 102 (9–300) μU ml −1 after 60 min and 74 (17–25) μU ml −1 after 2h. Plasma glucose was 4.3 (3.6–4.7) mmol l −1 at time 0 and 8.1 (2.0–10.3) and 6.2 (4–9.8) mmol 1 −1 after 60 and 2 h respectively. During OGTT growth hormone levels were 1.8 mU l −1 at time 0 and fell gradually to 0.8 mU l −1 after 90 min and were 1.1 (0.6–11) at 2h. During ITT growth hormone rose from 1.0 mU I −1 at time 0 to 50.5 mU 1 −1 after 60min. There were no changes in insulin-like growth factor-1 in either group. PAI-1 concentrations were 31.1 ng ml −1 at time 0 and showed a gradual fall to 22.3 and 18 ng ml −1 after 60 and 120min of OGTT. During ITT PAI-1 was 15.4ng ml −1 at time 0 and 14.8 and 18.4ng ml −1 after 60 and 90min. The results confirm that exogenous insulin does not acutely regulate PAW concentrations. The high portal (endogenous) insulin concentrations seen during OGTT in these patients do not seem to have measurable effects on hepatic PAI-1 output.