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Regulation of IRS-2 signaling by IGF-1 receptor in the diabetic rat heart.

Authors: Jiang, Y  Steinle, JJ 
Citation: Jiang Y and Steinle JJ, Can J Physiol Pharmacol. 2010 May;88(5):553-61.
Pubmed: (View Article at PubMed) PMID:20555424
DOI: Full-text: DOI:10.1139/y10-006

Cardiovascular disease involves changes in inflammatory markers. Since insulin/insulin-like growth factor 1 receptor (IGF-1R) can activate vascular endothelial growth factor to promote vascular growth, reduced IGF-1R signaling in the type I diabetic heart could be detrimental, leading to reduced, collateral blood vessel growth. This study assessed whether diabetes can induce an inflammatory phenotype to regulate molecules in the IGF-1 signaling cascade, thus mediating apoptosis. Rats were made diabetic using streptozotocin (to render them type I diabetic) for 2 months with no insulin treatment. At 2 months, rats were sacrificed under anesthesia, and the left ventricle was immediately removed and placed into cold lysis buffer for protein analyses. Western blotting, immunoprecipitation, and enzyme-linked immunosorbent assay analyses were completed to evaluate protein levels. Diabetes increased TNF-alpha, interleukin-6 (IL-6), and IL-1alpha levels in the heart. JNK and p42/p44 activity was significantly increased in the diabetic heart, while IGF-1R phosphorylation, IRS-2 tyrosine phosphorylation, and Akt activities were reduced. A significant increase in Bad protein levels and the cleavage of caspase 3 was observed in the diabetic heart. These results suggest that diabetes activates multiple inflammatory markers in the heart, which then signal a decrease in the activities of key players in the insulin-signaling cascade, namely IGF-1R, IRS-2, and Akt, to regulate apoptosis.


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CRRD Object Information
CRRD ID: 4142788
Created: 2010-09-08
Species: All species
Last Modified: 2010-09-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.