SummaryClinical studies have shown that plasma insulin levels are closely related to plasma plasminogen activator inhibitor 1 (PAI-1) levels. To investigate a possible involvement of hepatocytes we have studied the effect of insulin on PAI-1 production by primary cultures of human hepatocytes. We have isolated human hepatocytes from seven left liver lobes. PAI-1 activity measured in 24 hours conditioned medium varied considerably between the various hepatocyte preparations (from 2.9 to 8.5 units per 5 cm2of cells) possibly as a result of interindividual variability in basal PAI-1 production by hepatocytes from different donors. In all cases, however, the relative extent, time profile and dose-dependency of the insulin-induced increase in PAI-1 synthesis were consistent. Up to about 7 nM, insulin dose-dependently increased both PAI-1 activity and PAI-1 antigen production. The increase in PAI-1 synthesis became measurable between 4 and 8 hours after addition of the hormone, and maximally reached twofold control values. The increase in PAI-1 synthesis could be fully explained by a concomitant increase in PAI-1 mRNA levels. The effect of insulin seems fairly specific for the synthesis of PAI-1: overall protein synthesis and mRNA levels of some control proteins (albumin and fibrinogen) did not markedly change after insulin addition. These results, obtained with primary cultures of human hepatocytes, are fully comparable with those obtained with the hepatocellular carcinoma cell line Hep G2. They strengthen the suggestion that the elevated level of PAI-1 in high insulin plasma might be the result of increased hepatic synthesis of PAI-1.

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Haem-oxygenase-1 (HO-1) is an antioxidant stress protein that is mainly induced by reactive oxygen species, inflammatory cytokines and hyperthermia. We assessed the influence of different types of exercise on HO-1 expression in leukocytes of the peripheral blood in three groups of male participants: a short exhaustive run above the lactate steady state (n = 15), eccentric exercise (n = 12) and an intensive endurance run (half-marathon, n = 12). Blood samples were taken at rest and up to 24 h after exercise. Blood lactate concentration after exercise was 9.0 +/- 2.1, 3.8 +/- 1.6 and 5.1 +/- 2.2 mmol x l(-1) (mean +/- s) for the exhaustive run, eccentric exercise and half-marathon groups, respectively (P < 0.05). Creatine kinase concentration was highest 24 h after exercise: 133 +/- 91, 231 +/- 139 and 289 +/- 221 U x l(-1) for the exhaustive run, eccentric exercise and half-marathon groups, respectively (P < 0.05). The maximal increase in leukocyte counts after exercise was 11.5 +/- 19.2, 6.2 +/- 1.4 and 14.7 +/- 2.1 x 10(9) x l(-1). There was no change in HO-1 as a result of the short exhaustive run or the eccentric exercise, whereas the half-marathon had a significant stimulatory effect on HO-1-expression in lymphocytes, monocytes and granulocytes (P < 0.001) using flow cytometry analyses. In conclusion, eccentric exercise alone or short-term heavy exercise are not sufficient to stimulate the antioxidative stress protein HO-1 in peripheral leukocytes