# Mixed circuit training as a non-pharmacological strategy to improve platelet function and oxidative balance in type 2 diabetes: role of purinergic signaling

**Authors:** Lucas Macedo Chaves, Samantha Nuncio Prestes, André Campos De Lima, Aline Mânica, Daniela Zanini, Sedinei Lopes Copatti, Clodoaldo Antônio De Sá, Andréia Machado Cardoso

PMC · DOI: 10.1007/s11302-026-10136-8 · Purinergic Signalling · 2026-03-17

## TL;DR

This study shows that mixed circuit training can improve platelet function and reduce oxidative stress in women with type 2 diabetes.

## Contribution

The novel contribution is demonstrating how mixed circuit training modulates purinergic signaling and oxidative balance in T2DM patients.

## Key findings

- MCT reduced platelet ectonucleotidase activity and extracellular ATP levels, indicating modulated purinergic signaling.
- Exercise increased antioxidant defenses through higher GST activity and vitamin C levels, while lowering MPO activity.
- The results suggest a biochemical shift relevant to thromboinflammatory pathways in T2DM patients.

## Abstract

This study investigates the impact of a 16-week mixed circuit training (MCT) program on purinergic signaling and oxidative stress markers in women with type 2 diabetes mellitus (T2DM), focusing on its potential to modulate platelet-related purinergic signaling and oxidative stress markers that are mechanistically linked to platelet activation. A total of 21 women with T2DM and 23 non-diabetic controls, all sedentary and middle-aged, underwent MCT twice weekly. Biochemical, hemodynamic, and oxidative stress parameters, along with platelet ectonucleotidase activity and extracellular ATP levels, were assessed pre- and post-intervention. MCT significantly decreased ectonucleotidase diphosphohydrolase (E-NTPDase) activity for ADP hydrolysis in platelets, along with a reduction in extracellular ATP levels, indicating a modulation of purinergic signaling. Additionally, exercise enhanced antioxidant defenses, increasing glutathione-S-transferase (GST) activity and vitamin C levels, while reducing myeloperoxidase (MPO) activity, a key pro-oxidant enzyme. These changes suggest a shift toward a biochemical profile that may be relevant to thromboinflammatory pathways; however, no direct measures of platelet aggregation were performed. Mixed circuit training emerges as a valuable non-pharmacological strategy for improving oxidative balance and modulating purinergic markers in women with T2DM, warranting future studies including functional platelet assays and clinical outcomes.

## Linked entities

- **Proteins:** GSTU5 (glutathione S-transferase tau 5)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ENTPD8 (ectonucleoside triphosphate diphosphohydrolase 8) [NCBI Gene 377841] {aka E-NTPDase, GLSR2492, NTPDase-8, UNQ2492}, MPO (myeloperoxidase) [NCBI Gene 4353], GSTK1 (glutathione S-transferase kappa 1) [NCBI Gene 373156] {aka GST, GST 13-13, GST13, GST13-13, GSTK1-1, hGSTK1}, SLC16A1 (solute carrier family 16 member 1) [NCBI Gene 6566] {aka HHF7, MCT, MCT1, MCT1D}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, ALB (albumin) [NCBI Gene 280717]
- **Diseases:** metabolic syndrome (MESH:D024821), cardiovascular disease (MESH:D002318), hyperglycemia (MESH:D006943), erectile dysfunction (MESH:D007172), thrombosis (MESH:D013927), inflammatory (MESH:D007249), Diabetes (MESH:D003920), atherosclerosis (MESH:D050197), retinopathy (MESH:D058437), neuropathy (MESH:D009422), hyperglycemic (MESH:D006944), metabolic imbalances (MESH:D008659), TG (MESH:C566031), insulin resistance (MESH:D007333), coagulation (MESH:D001778), vascular dysfunction (MESH:D002561), nephropathy (MESH:D007674), deaths (MESH:D003643), T2DM (MESH:D003924), platelet aggregation (MESH:D001791)
- **Chemicals:** ATP (MESH:D000255), Adenosine (MESH:D000241), 2,4-dinitrophenylhydrazine (MESH:C004787), metformin (MESH:D008687), Ascorbic acid (MESH:D001205), dehydroascorbic acid (MESH:D003683), MgCl2 (MESH:D015636), T-SH (MESH:D013972), sodium citrate (MESH:D000077559), HEPES (MESH:D006531), NaCl (MESH:D012965), Lipid (MESH:D008055), glucose (MESH:D005947), nucleotide (MESH:D009711), H2SO4 (MESH:C033158), TG (MESH:D014280), ADP (MESH:D000244), CaCl2 (MESH:D002122), free fatty acids (MESH:D005230), trichloroacetic acid (MESH:D014238), prostaglandin E1 (MESH:D000527), EDTA (MESH:D004492), 2-nitrobenzoic acid (-), ROS (MESH:D017382), cholesterol (MESH:D002784), inorganic phosphate (MESH:D010710), calcium (MESH:D002118), d-luciferin (MESH:C532924), citrate (MESH:D019343), ATA (MESH:D000640), phospholipid (MESH:D010743), phenol (MESH:D019800), thiol (MESH:D013438), blood glucose (MESH:D001786), Pi (MESH:D010716), KCl (MESH:D011189), cAMP (MESH:D000242), malachite green (MESH:C005095), 4-aminoantipyrine (MESH:D000675), gliclazide (MESH:D005907), H2O2 (MESH:D006861), AMP (MESH:D000249)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913]

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12996453/full.md

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Source: https://tomesphere.com/paper/PMC12996453