Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle

Abstract

Insulin resistance onset in skeletal muscle is characterized by the impairment of insulin signaling, which reduces the internalization of glucose, known as glucose uptake, into the cell. Therefore, there is a deficit of intracellular glucose, which is the main source for energy production in the cell. This may compromise cellular viability and functions, leading to pathological dysfunction. Skeletal muscle fibers continuously generate reactive oxygen and nitrogen species (RONS). An excess of RONS produces oxidative distress, which may evoke cellular damage and dysfunction. However, a moderate level of RONS, which is called oxidative eustress, is critical to maintain, modulate and regulate cellular functions through reversible interactions between RONS and the components of cellular signaling pathways that control those functions, such as the facilitation of glucose uptake. The skeletal muscle releases peptides called myokines that may have endocrine and paracrine effects. Some myokines bind to specific receptors in skeletal muscle fibers and might interact with cellular signaling pathways, such as PI3K/Akt and AMPK, and facilitate glucose uptake. In addition, there are cytokines, which are peptides produced by non-skeletal muscle cells, that bind to receptors at the plasma membrane of skeletal muscle cells and interact with the cellular signaling pathways, facilitating glucose uptake. RONS, myokines and cytokines might be acting on the same signaling pathways that facilitate glucose uptake in skeletal muscle. However, the experimental studies are limited and scarce. The aim of this review is to highlight the current knowledge regarding the role of RONS, myokines and cytokines as potential signals that facilitate glucose uptake in skeletal muscle. In addition, we encourage researchers in the field to lead and undertake investigations to uncover the fundamentals of glucose uptake evoked by RONS, myokines, and cytokines.

Impact of Sarcopenia on Non-Alcoholic Fatty Liver Disease

“…Skeletal muscle plays a major role in glucose transport and processing, fatty acid oxidation, and energy homeostasis, all being key determinants in the pathophysiology of NAFLD [ 32 , 33 , 34 ]. Orally ingested proteins are broken down into amino acids and peptides by the action of digestive juices (especially gastric and pancreatic juices) and absorbed via the small intestine.…”

Nutrición animal: Texto de formación universitaria

“…La concepción del pasado atribuía a las RONS efectos adversos sobre el organismo, a causa del daño oxidativo a las biomoléculas y el desarrollo de una variedad de enfermedades; sin embargo, las nuevas evidencias sugieren que las RONS intracelulares son componentes importantes de las cascadas de señalización intracelular (Weidinger & Kozlov, 2015). Las fibras del músculo esquelético generan continuamente especies reactivas de oxígeno y nitrógeno RONS, donde un exceso produce estrés oxidativo, que puede causar daño y disfunción celular; sin embargo, un nivel moderado, que se denomina eustrés oxidativo, es fundamental para mantener, modular y regular las funciones celulares a través de interacciones reversibles entre RONS y los componentes de las vías de señalización celular que controlan esas funciones, como la facilitación de la captación de glucosa (Llanos & Palomero, 2022).…”

“…Reacción de Fenton: en 1894, donde demostró que el peróxido de hidrógeno (H2O2), catalizada por la sal ferrosa (Fe 2+ ), genera el radical hidroxilo (•OH), un oxidante fuerte y tóxico (Barbusiński, 2009). La reacción de Fenton fue la base para la comprensión del concepto de radicales libres, las especies reactivas de oxígeno (ROS), las especies reactivas de nitrógeno (RNS), y las especies reactivas de oxígeno y nitrógeno (RONS), como entidades químicas con un rol dual en los sistemas biológicos vivientes, necesarias para la salud y la vida, así como nocivos en dosis altas, tanto en los organismos vegetales (Mandal et al, 2022;Griffo et al, 2023), como animales y humanos (Lushchak & Lushchak, 2021;Ushio-Fukai et al, 2021;Llanos & Palomero, 2022).…”

The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment

“…Glucose disposal is mediated by the effect of insulin on its receptors on the cell surfaces of insulin-sensitive tissues, particularly skeletal muscle, adipose tissues, and the liver [ 12 , 13 ]. Once the insulin receptor is activated, glucose transport over the plasma membrane occurs through different members of the glucose transporter (GLUT) family, such as GLUT 4, which is expressed in skeletal muscle and adipose tissue, and GLUT2, which is expressed in the liver [ 14 ].…”