Siewiera 2022 Int J Mol Sci

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Publications in the MiPMap
Siewiera K, Labieniec-Watala M, Kassassir H, Wolska N, Polak D, Watala C (2022) Potential role of mitochondria as modulators of blood platelet activation and reactivity in diabetes and effect of metformin on blood platelet bioenergetics and platelet activation.

Β» Int J Mol Sci 23:3666. PMID: 35409027 Open Access

Siewiera Karolina, Labieniec-Watala Magdalena,  Kassassir Hassan,  Wolska Nina,  Polak Dawid,  Watala Cezary (2022) Int J Mol Sci

Abstract: Blood platelet dysfunctions are strongly involved in the development of the micro- and macrovascular complications in diabetes mellitus (DM). However, the molecular causes of abnormal platelet activation in DM remain unclear. Experimental data suggests that platelet mitochondria can regulate the prothrombotic phenotype of platelets, and changes in these organelles may influence platelet activation and modify platelet responses to stimulation. The present study evaluates the impact of DM on mitochondrial respiratory parameters and blood platelet activation/reactivity in a rat model of experimental diabetes following 1, 2.5 and 5 months of streptozotocin (STZ)-induced diabetes. Moreover, a mild inhibition of the mitochondrial respiratory chain with the use of metformin under in vitro and in vivo conditions was tested as a method to reduce platelet activation and reactivity. The platelets were studied with a combination of flow cytometry and advanced respirometry. Our results indicate that prolonged exposure of blood platelets to high concentrations of glucose, as in diabetes, can result in elevated blood platelet mitochondrial respiration; this may be an effect of cell adaptation to the high availability of energy substrates. However, as these alterations occur later than the changes in platelet activation/reactivity, they may not constitute the major reason for abnormal platelet functioning in DM. Moreover, metformin was not able to inhibit platelet activation and reactivity under in vitro conditions despite causing a decrease in mitochondrial respiration. This indicates that the beneficial effect of metformin on the coagulation system observed in vivo can be related to other mechanisms than via the inhibition of platelet activation. β€’ Keywords: Blood platelets, Diabetes mellitus, Metformin, Mitochondria, Mitochondrial respiration, Platelet activation, Platelet reactivity β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: PL Lodz Watala C

Labels: MiParea: Respiration  Pathology: Diabetes 

Organism: Rat  Tissue;cell: Platelet  Preparation: Permeabilized cells, Intact cells 

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2022-11, Metformin 

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