Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/174324
Title: | Disrupted mitochondrial and metabolic plasticity underlie comorbidity between age-Related and degenerative disorders as parkinson disease and type 2 diabetes mellitus. |
Author: | Juárez Flores, Diana Luz Ezquerra, 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 |
Keywords: | Malaltia de Parkinson Diabetis Comorbiditat Mitocondris Parkinson's disease Diabetes Comorbidity Mitochondria |
Issue Date: | 30-Oct-2020 |
Publisher: | MDPI |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/antiox9111063 |
It is part of: | Antioxidants, 2020, vol. 9, num. 11 |
URI: | http://hdl.handle.net/2445/174324 |
Related resource: | https://doi.org/10.3390/antiox9111063 |
ISSN: | 2076-3921 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
704520.pdf | 2.35 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License