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Reduced expression of insulin receptors in the kidneys of insulin-resistant rats.

Abstract
Insulin resistance is accompanied by hyperinsulinemia and activation of the renin-angiotensin system, both of which are associated with hypertension. Because the kidney plays a major role in the regulation of blood pressure, we studied the regulation of insulin receptor expression in the kidney during states of insulin resistance. Using two rat models of insulin resistance, Western blot analysis demonstrated a significant reduction in the expression of insulin receptor subunits in the kidney compared to lean control rats. Treatment of insulin resistance in Zucker rats with the insulin-sensitizing drug rosiglitazone partially restored renal insulin receptor levels. Conversely, treatment with the angiotensin II type 1 receptor (AT1) antagonist candesartan increased renal insulin receptor expression compared to untreated rats. Streptozotocin-induced hyperglycemia, which results from hypoinsulinemia, reduced expression of renal insulin receptors. Hyperinsulinemia induced by insulin infusion, however, did not produce a similar effect. In conclusion, insulin receptors are downregulated in the kidneys of insulin resistant rats, possibly mediated by hyperglycemia and angiotensin II.
AuthorsSwasti Tiwari, Veerendra K M Halagappa, Shahla Riazi, Xinqun Hu, Carolyn A Ecelbarger
JournalJournal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 18 Issue 10 Pg. 2661-71 (Oct 2007) ISSN: 1046-6673 [Print] United States
PMID17855644 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Hypoglycemic Agents
  • PPAR gamma
  • Receptor, Angiotensin, Type 1
  • Thiazolidinediones
  • Rosiglitazone
  • Receptor, Insulin
Topics
  • Animals
  • Gene Expression (drug effects)
  • Hyperinsulinism (drug therapy, metabolism)
  • Hypoglycemic Agents (pharmacology, therapeutic use)
  • Insulin Resistance
  • Kidney (drug effects, metabolism)
  • Male
  • PPAR gamma (agonists)
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Rats, Zucker
  • Receptor, Angiotensin, Type 1 (metabolism)
  • Receptor, Insulin (metabolism)
  • Rosiglitazone
  • Thiazolidinediones (pharmacology, therapeutic use)

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