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Related Experiment Videos

Hyperglycemia increases vascular adrenomedullin expression.

M Hayashi1, T Shimosawa, T Fujita

  • 1School of Medicine, University of Tokyo, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo, 112-8688, Japan. HAYASIMI-DIS@h.u-tokyo.ac.jp

Biochemical and Biophysical Research Communications
|May 18, 1999
PubMed
Summary

Hyperglycemia elevates vascular adrenomedullin (AM) expression via a protein kinase C (PKC)-dependent pathway. This glucose-induced vascular AM contributes to increased plasma AM levels in hyperglycemic patients.

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Area of Science:

  • Endocrinology
  • Vascular Biology
  • Metabolic Syndrome

Background:

  • Plasma adrenomedullin (AM) is elevated in hyperglycemic patients.
  • The vasculature is a primary site for AM production.
  • Understanding hyperglycemia's impact on vascular AM is crucial for diabetic complications.

Purpose of the Study:

  • To investigate the effect of hyperglycemia on AM expression in the vasculature.
  • To elucidate the signaling pathway involved in glucose-induced AM production.
  • To determine if vascular AM contributes to elevated plasma AM levels.

Main Methods:

  • Compared AM mRNA levels in aortas of diabetic and control rats.
  • Cultured vascular smooth muscle cells (VSMC) exposed to varying glucose concentrations.

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  • Assessed protein kinase C (PKC) activity in VSMC.
  • Utilized PKC inhibitors to block AM mRNA increase.
  • Main Results:

    • Diabetic rats exhibited higher aortic AM mRNA levels than controls.
    • High glucose concentrations (450 mg/dl) increased AM mRNA and PKC activity in VSMC.
    • PKC inhibition prevented the glucose-induced rise in AM mRNA.
    • Mannitol, an osmotic control, did not affect AM expression.

    Conclusions:

    • Hyperglycemia stimulates vascular AM expression through a PKC-dependent pathway.
    • Elevated plasma AM in hyperglycemia likely originates from increased vascular AM production.
    • Vascular AM may play a role in the pathogenesis of diabetic vascular complications.