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Published ahead of print on September 12, 2007
J Am Soc Nephrol 18: 2661-2671, 2007
© 2007 American Society of Nephrology
doi: 10.1681/ASN.2006121410
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BASIC RESEARCH

Reduced Expression of Insulin Receptors in the Kidneys of Insulin-Resistant Rats

Swasti Tiwari*, Veerendra K.M. Halagappa*, Shahla Riazi*, Xinqun Hu* and Carolyn A. Ecelbarger*,{dagger}

* Division of Endocrinology and Metabolism, Department of Medicine, {dagger} Center for the Study of Sex Differences in Health, Aging, and Disease, Georgetown University, Washington, DC

Correspondence: Dr. Swasti Tiwari or Dr. Carolyn A. Ecelbarger, Department of Medicine, Georgetown University, Box 571412, Washington, DC 20057-1412. Phone: 202-687-0653; Fax: 202-687-2040; E-mail: st285{at}georgetown.edu or ecelbarc{at}georgetown.edu

Received for publication December 28, 2006. Accepted for publication May 24, 2007.

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.




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 Proc. Natl. Acad. Sci. USAHome page
S. Tiwari, N. Sharma, P. S. Gill, P. Igarashi, C. R. Kahn, J. B. Wade, and C. M. A. Ecelbarger
Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor
PNAS, April 29, 2008; 105(17): 6469 - 6474.
[Abstract] [Full Text] [PDF]


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