Long-term aerobic exercise training in type two diabetic patients alters the expression of miRNA-223 and its corresponding target,the P2RY12 receptor,attenuating platelet function

Abstract

BACKGROUND:

Type two diabetes mellitus (T2DM) patients are prone to develop atherothrombotic events due to platelet hyper-reactivity stemming from platelet miRNA-223 down-regulation and over-expression of its corresponding target, P2RY12.

OBJECTIVE:

The study sought to determine the effects of long-term aerobic training on the expression levels of miRNA-223 and P2RY12 mRNA, and platelet function in T2DM patients.

METHODS:

Twenty-four patients with T2DM (age, 60.0±2.8 yrs.) were selected and randomly divided into two groups: aerobic exercise training (AET, n = 12) and control (CON, n = 12). The AET protocol was performed with moderate intensity for 12 weeks, while patients in the CON group followed their usual routine. Weight, body mass index (BMI), peak oxygen consumption (VO_2peak), lipid profile, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), platelet miRNA-223 and P2RY12 expression were measured before and after the period.

RESULTS:

There was a significant improvement in body weight, BMI, VO_2peak, FBG, HbA1c, and HOMA-IR, after 12 weeks of AET (P < 0.01). Platelet aggregation decreased significantly after 12 weeks in the AET group compared with the CON (P < 0.001) group. Platelets’ miRNA-223 and P2RY12 were significantly up- and down-regulated after AET in comparison with the CON group (P < 0.05), respectively. Moreover, the relative expression of miRNA-223 and P2RY12 significantly correlated with FBG changes following the intervention.

CONCLUSIONS:

It can be concluded that long-term moderate-intensity aerobic training might be effective for reducing the occurrence of atherothrombotic events leading to premature death in T2DM patients through the modulation of miRNA-223, P2RY12 receptor expression, and platelet function.