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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis*
  • Cells, Cultured
  • Cytochromes c / metabolism*
  • DNA Fragmentation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Humans
  • Insulin-Like Growth Factor I / agonists*
  • Insulin-Like Growth Factor I / genetics
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • RNA, Small Interfering / genetics


  • RNA, Small Interfering
  • Insulin-Like Growth Factor I
  • Cytochromes c
  • Glucose