Stimulation of PAI-1 and adipokines by glucose in human adipose tissue in vitro.
Adipokines such as Plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are elevated in patients with obesity, insulin resistance, and type 2 diabetes. In the present study, we investigated whether glucose affected the production of these adipokines in human adipose tissue in vitro. Glucose (up to 35mM) increased secretion of PAI-1 (p<0.01) and IL-8 (p<0.01), but not TNF-alpha, in a dose- and time-dependent manner. Half-maximal stimulatory concentration of glucose was about 1mM. Glucosamine (5mM) decreased production of PAI-1 (p<0.05) and IL-8 (p<0.05), indicating that the hexosamine biosynthesis pathway is not involved in the glucose-induced increment in adipokine secretion. The present data demonstrate that glucose increases PAI-1 and IL-8 secretion. However, glucose concentrations above 5mM had no additional effects on adipokine secretion, suggesting that mechanisms other than diabetes/insulin resistance-related hyperglycemia may be involved in the observed elevation of these adipokines.
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G
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Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Bruun
J M
JM
Lihn
A S
AS
Pedersen
S B
SB
Richelsen
B
B
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D018925:Chemokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005944:Glucosamine / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018925:Chemokines; D007328:Insulin; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose; D005944:Glucosamine