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2020-10-30

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cc-by (c) Juárez Flores, Diana Luz et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174324

Disrupted mitochondrial and metabolic plasticity underlie comorbidity between age-Related and degenerative disorders as parkinson disease and type 2 diabetes mellitus.

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https://doi.org/10.3390/antiox9111063

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Idiopathic Parkinson's disease (iPD) and type 2 diabetes mellitus (T2DM) are chronic, multisystemic, and degenerative diseases associated with aging, with eventual epidemiological co-morbidity and overlap in molecular basis. This study aims to explore if metabolic and mitochondrial alterations underlie the previously reported epidemiologic and clinical co-morbidity from a molecular level. To evaluate the adaptation of iPD to a simulated pre-diabetogenic state, we exposed primary cultured fibroblasts from iPD patients and controls to standard (5 mM) and high (25 mM) glucose concentrations to further characterize metabolic and mitochondrial resilience. iPD fibroblasts showed increased organic and amino acid levels related to mitochondrial metabolism with respect to controls, and these differences were enhanced in high glucose conditions (citric, suberic, and sebacic acids levels increased, as well as alanine, glutamate, aspartate, arginine, and ornithine amino acids; p-values between 0.001 and 0.05). The accumulation of metabolites in iPD fibroblasts was associated with (and probably due to) the concomitant mitochondrial dysfunction observed at enzymatic, oxidative, respiratory, and morphologic level. Metabolic and mitochondrial plasticity of controls was not observed in iPD fibroblasts, which were unable to adapt to different glucose conditions. Impaired metabolism and mitochondrial activity in iPD may limit energy supply for cell survival. Moreover, reduced capacity to adapt to disrupted glucose balance characteristic of T2DM may underlay the co-morbidity between both diseases. Conclusions: Fibroblasts from iPD patients showed mitochondrial impairment, resulting in the accumulation of organic and amino acids related to mitochondrial metabolism, especially when exposed to high glucose. Mitochondrial and metabolic defects down warding cell plasticity to adapt to changing glucose bioavailability may explain the comorbidity between iPD and T2DM.

Matèries

Malaltia de Parkinson, Diabetis, Comorbiditat, Mitocondris

Matèries (anglès)

Parkinson's disease, Diabetes, Comorbidity, Mitochondria

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

JUÁREZ FLORES, Diana luz, EZQUERRA TRABALÓN, Mario, GONZÁLEZ CASACUBERTA, Ingrid, ORMAZABAL HERRERO, Aida, MORÉN NÚÑEZ, Constanza, TOLOSA, Eduardo, FUCHO SALVADOR, Raquel, GUITART MAMPEL, Mariona, CASADO, Mercedes, VALLDEORIOLA SERRA, Francesc, TORRE LARA, Joan de la, MUÑOZ GARCÍA, José esteban, TOBÍAS, Ester, COMPTA, Yaroslau, GARCÍA-GARCÍA, Francesc josep, GARCÍA RUIZ, Carmen, FERNÁNDEZ CHECA TORRES, José carlos, MARTÍ DOMÈNECH, Ma. josep, GRAU JUNYENT, Josep m. (josep maria), CARDELLACH, Francesc, ARTUCH IRIBERRI, Rafael, FERNÁNDEZ SANTIAGO, Rubén, GARRABOU TORNOS, Glòria. Disrupted mitochondrial and metabolic plasticity underlie comorbidity between age-Related and degenerative disorders as parkinson disease and type 2 diabetes mellitus.. _Antioxidants_. 2020. Vol. 9, núm. 11. [consulta: 13 de gener de 2026]. ISSN: 2076-3921. [Disponible a: https://hdl.handle.net/2445/174324]

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