Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway

Ilan Gabriely, Xiao Man Yang, Jane A. Cases, Xiao Hui Ma, Luciano Rossetti, Nir Barzilai

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalAtherosclerosis
Volume160
Issue number1
DOIs
StatePublished - 2002

Fingerprint

Hexosamines
Plasminogen Activator Inhibitor 1
Biosynthetic Pathways
Hyperglycemia
Adipose Tissue
Gene Expression
Glucose
Fats
Insulin
Glucosamine
Hyperinsulinism
Somatostatin
Sprague Dawley Rats

Keywords

  • Diabetes mellitus
  • Glucose
  • Hexosamine biosynthetic pathway
  • Insulin resistance
  • Obesity
  • Plasminogen activator inhibitor type-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway. / Gabriely, Ilan; Yang, Xiao Man; Cases, Jane A.; Ma, Xiao Hui; Rossetti, Luciano; Barzilai, Nir.

In: Atherosclerosis, Vol. 160, No. 1, 2002, p. 115-122.

Research output: Contribution to journalArticle

Gabriely, Ilan ; Yang, Xiao Man ; Cases, Jane A. ; Ma, Xiao Hui ; Rossetti, Luciano ; Barzilai, Nir. / Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway. In: Atherosclerosis. 2002 ; Vol. 160, No. 1. pp. 115-122.
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