Endocrine Abstracts

Introduction: The aim of our experimental study was to investigate the effect of both T2DM and metformin treatment on myocardial tolerance to ischemia-reperfusion injury and cardiac AMP-activated protein kinase (AMPK) activity.

Methods: The protocol included four groups: i) controls (n=13) – non-diabetic rats treated with i.p. vehicle injections for 3 days prior to the heart perfusion, ii) controls+metformin (CM; n=12) – non-diabetic rats treated with metformin (200 mg/kg) i.p. for 3 days prior to the perfusion, iii) T2DM (n=12) – diabetic animals receiving vehicle, iv) T2DM+metformin (T2DMM; n=7) – diabetic rats treated with metformin. In all groups, the hearts were subjected to 30-min global ischemia and 120-min reperfusion according to Langendorff followed by histochemical determination of infarct size. Phosphorylated α-AMPK was evaluated with western blot analysis.

Results: Infarct size and postischemic recovery of left ventricular function were not different between controls and CM-group. Infarct size in T2DM was significantly lower than in controls (24.4±7.6 vs 45.0±10.4%, respectively, P<0.01), which is indicative of the phenomenon of metabolic preconditioning in T2DM. At the same time in T2DMM group there was no appreciable effect on infarct size (37.7±8.3%). In comparison to controls, α-AMPK phosphorylation was significantly increased in T2DM and, to a lesser extent, in CM-animals. However, AMPK activity was not different between T2DM and T2DMM groups.

Conclusion: AMPK phosphorylation was increased in both T2DM and CM, but it did not provide a significant cardioprotection in CM group. Moreover, combination of T2DM and metformin treatment had not potentiated infarct-limiting effect of T2DM, meaning that AMPK activation by metabolic preconditioning is not additive to that seen with metformin treatment. As the diabetes may act through many different pathways in the cell the effect of diabetes was more manifested in ischemia tolerance improvement.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.