Effect of type-1 diabetes mellitus on the regulation of insulin and endothelin-1 receptors in rat hearts

Nuha Nuwayri-Salti, Chehade N. Karam, Wael A. Al Jaroudi, Julnar A. Usta, Wael M. Maharsy, Khalil M. Bitar, Anwar B. Bikhazi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

This project assesses the treatment role with insulin and (or) angiotensin II receptor subtype-1 (AT1-R) blocker (ARB) on insulin receptor and endothelin-1 receptor subtype (ETA-R and ETB-R) regulation in rat hearts suffering from insulin-dependent diabetes mellitus (IDDM). Animals were divided into 6 groups: groups 1, 3, and 5 were controls consisting of normal, diabetic (streptozotocin-treated, once at 0 time), and diabetic supplemented daily with insulin, respectively, whereas groups 2, 4, and 6 were the controls treated daily with losartan. One month after enrollment, rats were sacrificed and samples of cardiac tissue were snapped frozen for immunostaining and Western blotting. Insulin receptor density was observed to be upregulated in the cardiomyocytes of diabetic animals, but downregulated with insulin supplementation alone. Cotreatment with insulin and an ARB resulted in drastic increase in insulin-receptor density in the diabetic rats. In addition, expression of ETA-R in cardiomyocytes was upregulated and was consistently maintained within the various treatment modalities. However, ETB-R expression was significantly reduced in the diabetic group treated with both insulin and an ARB. The changes in the expression of the insulin, the ET A-RS, and the ETB-RS at the various sites of the myocardium and the effect of both insulin treatment and blockade of the AT 1-R explain the new benefits related to the halting of myocardial remodeling in IDDM rats.

Original languageEnglish (US)
Pages (from-to)215-224
Number of pages10
JournalCanadian Journal of Physiology and Pharmacology
Volume85
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

Keywords

  • Cardiomyopathy
  • Endothelin-1 receptors
  • Insulin receptor
  • Insulin-dependent diabetes mellitus
  • Receptor regulation

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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