Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1

Biochem Biophys Res Commun. 2008 Nov 21;376(3):548-52. doi: 10.1016/j.bbrc.2008.09.025. Epub 2008 Sep 16.


Glucose toxicity is an important initiator of cardiovascular disease, contributing to the development of cardiomyocyte death and diabetic complications. The present study investigated whether high glucose state could induce apoptosis of rat cardiomyocyte cell line H9C2 through microRNA regulated insulin-like growth factor (IGF-1) signaling pathway. Our data showed that H9C2 cells exposed to high glucose have increased miR-1 expression level, decreased mitochondrial membrane potential, increased cytochrome-c release, and increased apoptosis. Glucose induced mitochondrial dysfunction, cytochrome-c release and apoptosis was blocked by IGF-1. Using prediction algorithms, we identified 3'-untranslated regions of IGF-1 gene are the target of miR-1. miR-1 mimics, but not mutant miR-1, blocked the capacity of IGF-1 to prevent glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. In conclusion, our data demonstrate that IGF-1 inhibits glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis and IGF-1's effect is regulated by miR-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism
  • Animals
  • Apoptosis* / genetics
  • Base Sequence
  • Cell Line
  • Cytochromes c / metabolism
  • Gene Expression Regulation*
  • Glucose / toxicity*
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism
  • Membrane Potential, Mitochondrial / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitochondria, Heart / enzymology
  • Mitochondria, Heart / metabolism
  • Mutation
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Rats


  • 3' Untranslated Regions
  • MicroRNAs
  • Insulin-Like Growth Factor I
  • Cytochromes c
  • Glucose