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• W2028510530 abstract "We examined whether acute in vivo increases in either plasma glucose or insulin concentrations stimulate PAI-1 gene expression in fat tissue. We studied chronically catheterized unstressed and awake, lean (∼300 g, n=12) and obese (∼450 g, n=12) Sprague–Dawley rats. Hyperglycemia (∼ 18mM) was induced for 3 h by glucose infusion during a pancreatic clamp (somatostatin inhibited endogenous insulin secretion). Compared with equivalent saline infusion, hyperglycemia induced a 6–7 fold increase in PAI-1 gene expression in both lean and obese rats (P<0.001). When the rate of cellular glucose uptake was matched during a euglycemic hyperinsulinemic (∼60 μU/ml) clamp, PAI-1 gene expression in both obese and lean rats was proportionately and significantly increased (P<0.001). We further examined whether induction of the hexosamine biosynthetic pathway would mimic the effects of hyperglycemia and hyperinsulinemia on PAI-1 gene expression. Indeed, infusion of glucosamine (GlcN, 30 μmol/kg/min), induced a ∼3–4 fold increase (P<0.01) in PAI-1 gene expression in both lean and obese animals. While obese rats had a four times greater fat mass then the lean rats, PAI-1 gene expression remained significantly higher when expressed as per gram fat. Our results support the hypothesis that increased glucose uptake induces PAI-1 gene expression in adipose tissue, probably through the activation of the hexosamine biosynthetic pathway. These findings may account for some of the fibrinolytic alterations seen in obese type 2 diabetic humans." @default.
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• W2028510530 date "2002-01-01" @default.
• W2028510530 modified "2023-10-14" @default.
• W2028510530 title "Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway" @default.
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• W2028510530 doi "https://doi.org/10.1016/s0021-9150(01)00574-3" @default.
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