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Related Experiment Videos

Hyperglycemia modulates angiotensinogen gene expression.

I Gabriely1, X M Yang, J A Cases

  • 1Diabetes Research and Training Center, Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|August 17, 2001
PubMed
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Elevated angiotensinogen (AGT) gene expression in obesity and type 2 diabetes is linked to hypertension. Nutrient pulses, particularly hyperglycemia, activate AGT expression via the hexosamine pathway, while obese rats show insulin resistance to AGT suppression.

Area of Science:

  • Endocrinology
  • Metabolic Syndrome
  • Hypertension Research

Background:

  • Elevated plasma angiotensinogen (AGT) is observed in insulin-resistant conditions like obesity and type 2 diabetes mellitus (DM2), which are linked to hypertension.
  • The hexosamine biosynthetic pathway (HBP) acts as a sensor for intracellular nutrient availability.

Purpose of the Study:

  • To investigate if hyperinsulinemia or hyperglycemia modulate AGT gene expression in fat and liver.
  • To determine if obesity and insulin resistance are associated with abnormal AGT regulation.
  • To test the hypothesis that HBP activation acutely induces AGT gene expression in vivo.

Main Methods:

  • Studies were conducted on chronically catheterized lean and obese Sprague-Dawley rats.
  • Four clamp studies were performed: insulin clamp, pancreatic clamp for hyperglycemia, euglycemia with glucosamine (GlcN) infusion, and saline control.

Related Experiment Videos

  • AGT gene expression in fat and liver tissues was measured.

    • Main Results:

    • Insulin infusion suppressed AGT gene expression in lean rats but not in obese rats, indicating insulin resistance.
    • Hyperglycemia significantly activated AGT gene expression in both lean and obese rats (approximately threefold increase).
    • Glucosamine infusion mimicked the effect of hyperglycemia, increasing AGT gene expression (approximately twofold increase).

    Conclusions:

    • Physiological nutrient pulses, via HBP activation, acutely induce AGT gene expression in adipose tissue and liver.
    • Insulin resistance in obese rats may enhance nutrient-induced AGT gene expression.
    • Increased AGT gene expression could link obesity, insulin resistance, and hypertension.