Acta Diabetologica

, Volume 55, Issue 9, pp 893–899 | Cite as

Aerobic training improves platelet function in type 2 diabetic patients: role of microRNA-130a and GPIIb

  • Atousa Akbarinia
  • Mehdi KargarfardEmail author
  • Mahmood Naderi
Original Article



MicroRNAs (miRs) that are mediators of gene expression have been implicated in type 2 diabetes mellitus (T2DM). Platelet hyper-reactivity is one of the most important disorders in T2DM patients. In this study, we explored the effects of aerobic training (AT) on platelet aggregation and Glycoprotein IIb (GPIIb) receptor and miR-130a expression.


In a quasi-experimental controlled trial, 24 sedentary, eligible female participants with T2DM were selected (age 61.92 ± 3.63) and divided into AT and control (CON) groups based on their peak oxygen consumption (VO2peak). AT protocol was performed three times per week in non-consecutive days on a treadmill with mean intensity (60–75% VO2peak) for 8 weeks, while the control group refrained from any type of exercise training. Two blood samples were taken before and after this period. Real-time PCR was used to determine the expression of platelet GPIIb and miR-130a. Moreover, platelet indices (PLT, MPV, PDW, and PCT), collagen-induced platelet aggregation and glycemic variables were measured.


Analyses of data showed that anthropometric variables, VO2peak and glycemic control improved significantly (P < 0.01) after AT. Furthermore, MPV, PDW (P < 0.01), and platelet aggregation (P < 0.001) decreased significantly following AT compared with control group. Platelet GPIIb expression down-regulated significantly (P < 0.05) in AT group but up-regulation of miR-130a expression was not significant between two groups (P > 0.05).


Platelet hyper-reactivity in T2DM females might be decreased not only by glycemic control and amelioration of anthropometric and platelet indices, but also the down-regulation of GPIIb following AT. However, more research is needed to determine the effects of exercise training on platelet miR-130a.


Platelet indices GPIIb/IIIa MicroRNA-130a Exercise training Diabetes mellitus 



The authors have no conflicts of interest. The authors would also like to thank the study participants for their cooperation and dedication. We wish to thank from University of Isfahan (Isfahan, Iran) and Cell-Based Therapies Research Center, Digestive Disease Research Institute (Tehran, Iran) for their financial support.


This research received no specific grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Whiting DR, Guariguata L, Weil C, Shaw J (2011) IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 94(3):311–321CrossRefPubMedGoogle Scholar
  2. 2.
    Kakouros N, Rade JJ, Kourliouros A, Resar JR (2011) Platelet function in patients with diabetes mellitus: from a theoretical to a practical perspective. Int J Endocrinol 2011:742719CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Laakso M (2010) Cardiovascular disease in type 2 diabetes from population to man to mechanisms. Diabetes Care 33(2):442–449CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ferreiro JL, Angiolillo DJ (2010) Platelet abnormalities in diabetes mellitus. Diabetes Vasc Dis Res 7:251–259 (1479164110383994) CrossRefGoogle Scholar
  5. 5.
    Li Z, Delaney MK, O’Brien KA, Du X (2010) Signaling during platelet adhesion and activation. Arterioscler Thromb Vasc Biol 30(12):2341–2349CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Neki N (2004) Platelet glycoprotein IIb/IIIa receptor inhibitors–role in coronary artery disease. J Indian Acad Clin Med 5(3):259–265Google Scholar
  7. 7.
    Kalantzi KI, Tsoumani ME, Goudevenos IA, Tselepis AD (2012) Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives. Expert Rev Clin Pharmacol 5(3):319–336CrossRefPubMedGoogle Scholar
  8. 8.
    Wagner CL, Mascelli M, Neblock D, Weisman H, Coller B, Jordan R (1996) Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 88(3):907–914PubMedGoogle Scholar
  9. 9.
    Tschoepe D, Roesen P, Kaufmann L et al (1990) Evidence for abnormal platelet glycoprotein expression in diabetes mellitus. Eur J Clin Investig 20(2Part 1):166–170CrossRefGoogle Scholar
  10. 10.
    Razmara M, Hjemdahl P, Östenson CG, Li N (2008) Platelet hyperprocoagulant activity in Type 2 diabetes mellitus: attenuation by glycoprotein IIb/IIIa inhibition. J Thromb Haemost 6(12):2186–2192CrossRefPubMedGoogle Scholar
  11. 11.
    Roffi M, Chew DP, Mukherjee D et al (2001) Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation 104(23):2767–2771CrossRefPubMedGoogle Scholar
  12. 12.
    Lincoff AM (2003) Important triad in cardiovascular medicine diabetes, coronary intervention, and platelet glycoprotein IIb/IIIa receptor blockade. Circulation 107(11):1556–1559CrossRefPubMedGoogle Scholar
  13. 13.
    Stakos DA, Gatsiou A, Stamatelopoulos K, Tselepis AD, Stellos K (2013) Platelet microRNAs: from platelet biology to possible disease biomarkers and therapeutic targets. Platelets 24(8):579–589CrossRefPubMedGoogle Scholar
  14. 14.
    Edelstein LC, McKenzie S, Shaw C, Holinstat M, Kunapuli S, Bray P (2013) MicroRNAs in platelet production and activation. J Thromb Haemost 11(s1):340–350CrossRefPubMedGoogle Scholar
  15. 15.
    Garzon R, Pichiorri F, Palumbo T et al (2006) MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci USA 103(13):5078–5083CrossRefPubMedGoogle Scholar
  16. 16.
    Ding Y, Sun X, Shan P-F (2017) MicroRNAs and cardiovascular disease in diabetes mellitus. BioMed Res Int 2017:4080364PubMedPubMedCentralGoogle Scholar
  17. 17.
    Zampetaki A, Kiechl S, Drozdov I et al (2010) Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 107(6):810–817CrossRefPubMedGoogle Scholar
  18. 18.
    Duan X, Zhan Q, Song B et al (2014) Detection of platelet microRNA expression in patients with diabetes mellitus with or without ischemic stroke. J Diabetes Complic 28(5):705–710CrossRefGoogle Scholar
  19. 19.
    Marwick TH, Hordern MD, Miller T et al (2009) Exercise training for type 2 diabetes mellitus impact on cardiovascular risk: a scientific statement from the American Heart Association. Circulation 119(25):3244–3262CrossRefPubMedGoogle Scholar
  20. 20.
    Way KL, Hackett DA, Baker MK, Johnson NA (2016) The effect of regular exercise on insulin sensitivity in type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab J 40(4):253–271CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Boulé N, Kenny G, Haddad E, Wells G, Sigal R (2003) Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in Type 2 diabetes mellitus. Diabetologia 46(8):1071–1081CrossRefPubMedGoogle Scholar
  22. 22.
    Wang J-S, Chow S-E (2004) Effects of exercise training and detraining on oxidized low-density lipoprotein-potentiated platelet function in men. Arch Phys Med Rehabilit 85(9):1531–1537CrossRefGoogle Scholar
  23. 23.
    Cardoso AM, Bagatini MD, Martins CC et al (2012) Exercise training prevents ecto-nucleotidases alterations in platelets of hypertensive rats. Mol Cell Biochem 371(1–2):147–156CrossRefPubMedGoogle Scholar
  24. 24.
    Di Massimo C, Scarpelli P, Penco M, Tozzi-Ciancarelli M (2004) Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans. Eur J Appl Physiol 91(4):406–412CrossRefPubMedGoogle Scholar
  25. 25.
    De Meirelles L, Mendes-Ribeiro A, Mendes M et al (2009) Chronic exercise reduces platelet activation in hypertension: upregulation of the l-arginine-nitric oxide pathway. Scand J Med Sci Sports 19(1):67–74CrossRefPubMedGoogle Scholar
  26. 26.
    Ficicilar H, Zergeroglu A, Ersoz G, Erdogan A (2006) The effects of short-term training on platelet functions and total antioxidant capacity in rats. Physiol Res 55(2):151PubMedGoogle Scholar
  27. 27.
    Nielsen S, Åkerström T, Rinnov A et al (2014) The miRNA plasma signature in response to acute aerobic exercise and endurance training. PloS One 9(2):e87308CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Baggish AL, Hale A, Weiner RB et al (2011) Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol 589(16):3983–3994CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Association GAotWM (2014) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent 81 (3):14Google Scholar
  30. 30.
    Naderi M, Tehrani HA, Soleimani M, Shabani I, Hashemi SM (2015) A home-brew real-time PCR assay for reliable detection and quantification of mature miR-122. Appl Immunohistochem Mol Morphol 23(8):601–606CrossRefPubMedGoogle Scholar
  31. 31.
    Jorge MLMP, de Oliveira VN, Resende NM et al (2011) The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus. Metabolism 60(9):1244–1252CrossRefPubMedGoogle Scholar
  32. 32.
    Hawley J, Lessard S (2008) Exercise training-induced improvements in insulin action. Acta Physiol 192(1):127–135CrossRefGoogle Scholar
  33. 33.
    Randle P, Garland P, Hales C, Newsholme E (1963) The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 281(7285):785–789CrossRefGoogle Scholar
  34. 34.
    Yenigün EC, Okyay GU, Pirpir A, Hondur A, Yıldırım İS (2014) Increased mean platelet volume in type 2 diabetes mellitus. Dicle Tıp Dergisi 41(1):17–22CrossRefGoogle Scholar
  35. 35.
    Heber S, Volf I (2015) Effects of physical (in) activity on platelet function. BioMed Res Int 2015:165078CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Demirtunc R, Duman D, Basar M, Bilgi M, Teomete M, Garip T (2009) The relationship between glycemic control and platelet activity in type 2 diabetes mellitus. J Diabetes Complic 23(2):89–94CrossRefGoogle Scholar
  37. 37.
    Radom-Aizik S, Zaldivar FP, Haddad F, Cooper DM (2014) Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease. Brain Behav Immun 39:121–129CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Radom-Aizik S, Zaldivar F Jr, Oliver S, Galassetti P, Cooper DM (2010) Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes. J Appl Physiol 109(1):252–261CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Silva GJ, Bye A, el Azzouzi H, Wisløff U (2017) MicroRNAs as important regulators of exercise adaptation. Prog Cardiovasc Dis 60(1):130–151CrossRefPubMedGoogle Scholar
  40. 40.
    Russell AP, Lamon S, Boon H et al (2013) Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training. J Physiol 591(18):4637–4653CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Atousa Akbarinia
    • 1
  • Mehdi Kargarfard
    • 1
    Email author
  • Mahmood Naderi
    • 2
  1. 1.Department of Exercise Physiology, Faculty of Sport SciencesUniversity of IsfahanIsfahanIran
  2. 2.Cell-Based Therapies Research Center, Digestive Disease Research InstituteTehran University of Medical SciencesTehranIran

Personalised recommendations