Type 2 diabetes is a chronic disease in which the body does not make enough insulin, or does not use it effectively. It is caused by a combination of a genetic predisposition to obesity, a sedentary lifestyle, and an unhealthy diet. Researchers from the University of Barcelona (UB), the Institute for Research in Biomedicine (IRB Barcelona) and the Network Biomedical Research Center for Diabetes and Associated Metabolic Diseases (CIBERDEM), in Spain, have identified a molecular mechanism involved in the development of this disease that affects millions of people around the world.
The study has described —in patient samples and in animal models of type 2 diabetes— a decrease in mitochondrial proteins responsible for the synthesis of subunits of the cellular respiratory chain complexes. This decrease in proteins is associated with an increase in intracellular nitric oxide which, according to the researchers, could be a potential diagnostic method for the disease.
Mitochondria are the organelles responsible for the production of cellular energy and there is evidence linking dysfunctions in their functioning with the insulin resistance characteristic of type 2 diabetes. The objective of the study was to determine if there were alterations in the subunits of the complexes. of the mitochondrial respiratory chain that could be associated with this mitochondrial dysfunction. In addition, they also wanted to explore whether nitric oxide — a molecule present in mitochondria and which acts as a cellular messenger in various physiological and also pathological processes — could be involved in these alterations.
To do this, the researchers have analyzed muscle samples from obese patients with type 2 diabetes (which usually develops around age 55), obese patients with early-onset diabetes (which appears around age 25) and in an animal model. of diabetes. “In this study, carried out in collaboration with clinicians from the City University of Dublin and St James’s Hospital from Trinity College Dublin, in Ireland, and with researchers from IRB Barcelona, ”we have found that mtRNAs — the proteins responsible for synthesizing mitochondrial complexes—play a very relevant role in the defects observed in mitochondrial respiration, since their decrease leads to a decrease in the synthesis of specific subunits of the respiratory chain complexes and, therefore, mitochondrial dysfunction associated with a greater production of reactive oxygen species (ROS) and specifically nitric oxide”, explains Maribel Hernández-Alvarez, a researcher at the UB and CIBERDEM, who has led the study together with Antonio Zorzano (UB / IRB Barcelona / CIBERDEM).
Members of the research group led by Maribel Hernández-Alvarez. (Photo: University of Barcelona. CC BY)
These results open the door to research on the effects of enzymes that produce nitric oxide. They will also make it possible to study the effect of the abundance of mtRNA synthetases, and the relationship they have with the synthesis of mitochondrial proteins.
The study is titled “Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle”. And it has been published in the academic journal Redox Biology. (Source: University of Barcelona)