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Biochem Biophys Res Commun. 2009 Jun 26;384(2):259-64. doi: 10.1016/j.bbrc.2009.04.113. Epub 2009 May 4.

Insulin-like growth factor-1 receptor activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis.

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Texas Heart Institute and The University of Texas Medical School, Houston, TX 77030, USA.


Vascular disease is the leading cause of morbidity and mortality in patients with diabetes. Persistent hyperglycemia--the dominant metabolic derangement of diabetes, can cause endothelial cell apoptosis. Diabetes is often associated with low insulin like growth factor-1 (IGF-1), and the latter state has been linked to adverse risk profile and increased cardiovascular disease incidence. Since IGF-1 acts as an important survival factor for multiple cell types, this study was to investigate whether IGF-1 exert regulatory effects on high glucose-induced apoptosis of vascular endothelial cells. Exposure to high glucose dose- and time-dependently induced apoptotic changes (e.g., DNA fragmentation, altered mitochondrial membrane potential, and cytochrome-c release) in human umbilical vein endothelial cells (HUVECs). Addition of IGF-1 blocked the high glucose effect in a manner dependent on expression of IGF-1 receptor (IGF-1R) since silencing IGF-1R with small interference RNA could diminish the IGF-1' anti-apoptosis effect. Our findings show that enhanced IGF-1 signaling inhibits glucose-induced apoptosis in HUVECs by reducing mitochondrial dysfunction, and maintaining the mitochondrial retention of cytochrome-c. These results may have therapeutic implications in preventing/reducing diabetes associated endothelial dysfunction.

[Indexed for MEDLINE]

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