RGD Reference Report - Reduced expression of insulin receptors in the kidneys of insulin-resistant rats. - Rat Genome Database

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

Authors: Tiwari, S  Halagappa, VK  Riazi, S  Hu, X  Ecelbarger, CA 
Citation: Tiwari S, etal., J Am Soc Nephrol. 2007 Oct;18(10):2661-71. Epub 2007 Sep 12.
RGD ID: 2290475
Pubmed: PMID:17855644   (View Abstract at PubMed)
DOI: DOI:10.1681/ASN.2006121410   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOInsr (Rattus norvegicus)2290475; 2290475protein:decreased expression:kidneyRGD 
Experimental Diabetes Mellitus  IEP 2290475protein:decreased expression:kidneyRGD 
type 2 diabetes mellitus  ISOInsr (Rattus norvegicus)2290475; 2290475protein:decreased expression:kidneyRGD 
type 2 diabetes mellitus  IEP 2290475protein:decreased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)


Additional Information