Blunted Cardiac AMPK Response is Associated with Susceptibility to Ischemia/Reperfusion in Male Offspring of Gestational Diabetic Rats.

BACKGROUND/AIMS:Gestational diabetes mellitus (GDM) is closely associated with early perinatal complications and long-term health problems, such as cardiovascular disease, in offspring. AMP-activated protein kinase (AMPK) is cardioprotective, particularly in the treatment of ischemia/reperfusion (I/R). However, whether GDM programs offspring susceptibility to cardiac I/R and the involvement of AMPK remain unclear. METHODS:Streptozotocin was administered to rats during mid pregnancy; the postpartum maternal metabolome was assessed by chromatography-mass spectrometry (GC-MS). Male offspring were subjected to body composition scanning followed by ex vivo global I/R. Cardiac signaling was determined by Western blotting. RESULTS:The body weights (BWs) of the GDM male offspring were significantly heavier than those of the control group from the age of 8 weeks; the heart weights (HWs) and HW/BW were also increased in the GDM group compared to the control group. The ex vivo post-I/R cardiac contractile function recovery was significantly compromised in the GDM male offspring. The phosphorylation of AMPK and ACC was elevated by ex vivo I/R in both groups, but to a significantly lesser extent in the GDM group. CONCLUSION:GDM male offspring rats have higher risks of overgrowth and intolerance to cardiac I/R, which may be due to a compromised AMPK signaling pathway.