AMPK/mTOR-mediated therapeutic effect of metformin on myocardial ischaemia reperfusion injury in diabetic rat

Abstract

Background

The autophagy associated signalling pathways such as AMPK/mTOR previously were suggested to play a crucial role in protecting from ischaemia–reperfusion injury (IRI). The objective of this study was to evaluate the effect of metformin (DMBG) on autophagy during myocardial IRI with diabetes mellitus (DM).

Methods

The DM rat model was established using streptozocin, and further induced ischaemia model via transitory ligation of the left anterior coronary artery and following reperfusion. The model rats were treated with 400 mg/kg/day DMBG for 1 week. Autophagosomes were investigated using transmission electron microscopy. Autophagy-associated signalling pathways were detected by western blot.

Results

The myocardial infarct size was shown to significantly increase in the DM rats exposed to IRI compared to negative control, but decrease in DMBG treated. The mature autophagosomes were elevated in infarction and marginal zones of DM + IRI + DMBG compared to DM + IRI. Furthermore, the increasing protein levels of LC3-II, BECLIN 1, autophagy related 5 (ATG5) and AMP-activated protein kinase suggested activated autophagy-associated intracellular signalling AMPK and mTOR pathways upon DMBG treated.

Conclusions

Taken together, the outcomes determinate a novel mechanism that DMBG could activate autophagy process to provide a cardio-protective effect against DM induced myocardial IRI.

Keywords:

• Metformin
• diabetes
• myocardial ischaemia–reperfusion injury
• autophagy

Disclosure statement

The authors declare that they have no competing interests.

Author contributions

L. Z. participated in the design of the study, conducted the experiments and drafted the manuscript. X. Z., L. G. and J. G. collected and analysed the data. D. Z. designed the study, revised the manuscript and is responsible for authenticity of data. All authors read and approved the final manuscript.

Data availability statement

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Additional information

Funding

This project was supported by grants from Sub task of national key R & D plan [No. 2017YFC1104202]. The funder didn’t participation in the research.