Oncostatin M (OSM) protects against cardiac ischaemia/reperfusion injury in diabetic mice by regulating apoptosis, mitochondrial biogenesis and insulin sensitivity

J Cell Mol Med. 2015 Jun;19(6):1296-307. doi: 10.1111/jcmm.12501. Epub 2015 Mar 8.


Oncostatin M (OSM) exhibits many unique biological activities by activating Oβ receptor. However, its role in myocardial I/R injury in diabetic mice remains unknown. The involvement of OSM was assessed in diabetic mice which underwent myocardial I/R injury by OSM treatment or genetic deficiency of OSM receptor Oβ. Its mechanism on cardiomyocyte apoptosis, mitochondrial biogenesis and insulin sensitivity were further studied. OSM alleviated cardiac I/R injury by inhibiting cardiomyocyte apoptosis through inhibition of inositol pyrophosphate 7 (IP7) production, thus activating PI3K/Akt/BAD pathway, decreasing Bax expression while up-regulating Bcl-2 expression and decreasing the ratio of Bax to Bcl-2 in db/db mice. OSM enhanced mitochondrial biogenesis and mitochondrial function in db/db mice subjected to cardiac I/R injury. On the contrary, OSM receptor Oβ knockout exacerbated cardiac I/R injury, increased IP7 production, enhanced cardiomyocyte apoptosis, impaired mitochondrial biogenesis, glucose homoeostasis and insulin sensitivity in cardiac I/R injured diabetic mice. Inhibition of IP7 production by TNP (IP6K inhibitor) exerted similar effects of OSM. The mechanism of OSM on cardiac I/R injury in diabetic mice is partly associated with IP7/Akt and adenine mononucleotide protein kinase/PGC-1α pathway. OSM protects against cardiac I/R Injury by regulating apoptosis, insulin sensitivity and mitochondrial biogenesis in diabetic mice through inhibition of IP7 production.

Keywords: diabetes; inositol pyrophosphate 7; ischaemia/Reperfusion injury; oncostatin M.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Blotting, Western
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / physiopathology*
  • Glucose / metabolism
  • Homeostasis / genetics
  • Inositol Phosphates / antagonists & inhibitors
  • Inositol Phosphates / metabolism
  • Insulin Resistance*
  • Mice, 129 Strain
  • Mice, Knockout
  • Mice, Mutant Strains
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oncostatin M / pharmacology*
  • Organelle Biogenesis
  • Protective Agents / pharmacology
  • Receptors, Oncostatin M / genetics
  • Receptors, Oncostatin M / metabolism


  • Inositol Phosphates
  • Protective Agents
  • Receptors, Oncostatin M
  • Oncostatin M
  • Glucose