Does Metformin Modulate Mitochondrial Dynamics and Function in Type 2 Diabetic Patients?
Por:
Martinez de Marañón A, Canet FG, Abad-Jimenez Z, Jover A, Morillas C, Rocha M and Víctor VM
Publicada:
10 ago 2021
Ahead of Print:
1 mar 2021
Resumen:
Metformin is an effective drug against type 2 diabetes (T2D), a pathogenesis in which mitochondrial dysfunction is one of the main players. Thus, our first aim was to describe the effect of metformin on mitochondrial function in an outpatient population with T2D. For analyzing this hypothesis, we performed a preliminary cross-sectional study complying with the STROBE requirements. We studied leukocytes from 139 healthy controls, 39 T2D patients without metformin treatment, and 81 T2D patients who had been on said treatment for at least 1 year. Leukocytes from T2D patients displayed higher total and mitochondrial reactive oxygen species levels, lower mitochondrial membrane potential, and lower oxygen consumption. Moreover, their mitochondria expressed lower mRNA and protein levels of fusion proteins mitofusin-1 (MFN1), mitofusin-2 (MFN2), and optic atrophy 1 (OPA1), and higher protein and gene expression levels of mitochondrial fission protein 1 (FIS1) and dynamin-related protein 1 (DRP-1). In addition, we observed enhanced leukocyte/endothelial interactions in T2D patients. Metformin reversed most of these effects, ameliorating mitochondrial function and dynamics, and reducing the leukocyte/endothelial interactions observed in T2D patients. These results raise the question of whether metformin tackles T2D by improving mitochondrial dysfunction and regulating mitochondrial dynamics. Furthermore, it would seem that metformin modulates the alteration of interactions between leukocytes and the endothelium, a subclinical marker of early atherosclerosis.
Filiaciones:
:
University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain, Service of Endocrinology and Nutrition, Valencia, Comunidad Valenciana, Spain
amardema
:
University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Service of Endocrinology and Nutrition, Valencia, Valencia, Spain
francisco.canet.1994
:
University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Service of Endocrinology and Nutrition, Valencia, Spain
zaiaji
:
University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Service of Endocrinology and Nutrition, Valencia, Spain
anajover.endo
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University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain, Service of Endocrinology and Nutrition, Valencia, Spain
carlos.morillas
:
University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain, Service of Endocrinology and Nutrition, , Valencia, Comunidad Valenciana, Spain
University of Valencia, 16781, Department of Physiology, Valencia, Comunitat Valenciana, Spain
Milagros.Rocha
:
University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain, Service of Endocrinology and Nutrition, , Valencia, Comunidad Valenciana, Spain
University of Valencia, 16781, Department of Physiology, Valencia, Comunitat Valenciana, Spain
CIBERehd-University of Valencia, Department of Pharmacology, , Valencia, Spain
victor.victor
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