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Plasminogen activator inhibitor-1 expression and secretion are stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes.

Abstract：

:Various adipocytokines have been described which influence insulin sensitivity and vascular function profoundly and might, therefore, potentially link obesity, insulin resistance, and atherosclerosis. Among those, plasminogen activator inhibitor (PAI)-1 is an adipose-secreted factor upregulated in obesity and insulin resistance that inhibits fibrinolysis. Furthermore, recent studies in knockout mice suggest that PAI-1 directly impairs insulin sensitivity. In the current study, the impact of growth hormone (GH) and interleukin (IL)-6 on PAI-1 mRNA synthesis and secretion was determined in 3T3-L1 adipocytes. Interestingly, 500 ng/ml GH and 30 ng/ml IL-6 increased PAI-1 secretion five-fold and 3.6-fold, respectively. Furthermore, GH and IL-6 induced PAI-1 mRNA by up to 7.3-fold, and 3.6-fold, respectively, in a time-dependent fashion with significant stimulation seen at concentrations as low as 5 ng/ml GH and 10 ng/ml IL-6. Other insulin resistance-inducing hormones which stimulated PAI-1 synthesis included insulin, TNFalpha, and dexamethasone. Studies using pharmacological inhibitors suggested that basal and GH-induced PAI-1 synthesis were at least in part mediated by p44/42 mitogen-activated protein kinase but not janus kinase 2 and phosphatidylinositol 3-kinase. Taken together, our results show a differential regulation of PAI-1 mRNA by insulin resistance-inducing hormones including GH and IL-6.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Kralisch S,Klein J,Lossner U,Blüher M,Paschke R,Stumvoll M,Fasshauer M

doi

10.1016/j.mce.2006.04.027

subject

Has Abstract

pub_date

2006-07-11 00:00:00

pages

56-62

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(06)00221-8

journal_volume

253

pub_type

杂志文章

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