Hyperglycemia modulates angiotensinogen gene expression

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

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin-resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions that are directly correlated to hypertension. We examined whether hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression and whether obesity and insulin resistance are associated with abnormal AGT regulation. In addition, because the hexosamine biosynthetic pathway is considered to function as a biochemical sensor of intracellular nutrient availability, we hypothesized that activation of this pathway would acutely mediate in vivo the induction of AGT gene expression in fat and liver. We studied chronically catheterized lean (∼300 g) and obese (∼450 g) Sprague-Dawley rats in four clamp studies (η = 3/group), creating physiological hyperinsulinemia (∼60 μU/ml, by an insulin clamp), hyperglycemia (∼18 mM, by a pancreatic clamp using somatostatin to prevent endogenous insulin secretion), or euglycemia with glucosamine infusion (GlcN; 30 μmol·kg-1·min-1) and equivalent saline infusions (as a control). Although insulin infusion suppressed AGT gene expression in fat and liver of lean rats, the obese rats demonstrated resistance to this effect of insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene expression in fat and liver by approximately threefold in both lean and obese rats (P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results support the hypothesis that physiological nutrient "pulses" may acutely induce AGT gene expression in both adipose tissue and liver through the activation of the hexosamine biosynthetic pathway. Resistance to the suppressive effect of insulin on AGT expression in obese rats may potentiate the effect of nutrients on AGT gene expression. We propose that increased AGT gene expression and possibly its production may provide another link between obesity/insulin resistance and hypertension.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number3 50-3
StatePublished - 2001

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Angiotensinogen
Hyperglycemia
Gene Expression
Insulin
Fats
Liver
Hexosamines
Obesity
Biosynthetic Pathways
Hyperinsulinism
Food
Insulin Resistance
Hypertension
Glucosamine
Somatostatin
Type 2 Diabetes Mellitus
Sprague Dawley Rats
Adipose Tissue

Keywords

  • Glucosamine
  • Nutrient sensing

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Hyperglycemia modulates angiotensinogen gene expression. / Gabriely, Ilan; Yang, Xiao Man; Cases, Jane A.; Ma, Xiao Hui; Rossetti, Luciano; Barzilai, Nir.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 281, No. 3 50-3, 2001.

Research output: Contribution to journalArticle

Gabriely, Ilan ; Yang, Xiao Man ; Cases, Jane A. ; Ma, Xiao Hui ; Rossetti, Luciano ; Barzilai, Nir. / Hyperglycemia modulates angiotensinogen gene expression. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2001 ; Vol. 281, No. 3 50-3.
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