endothelin-1 and Sarcopenia

Diabetes and sarcopenia are verified as mutual relationships, which seriously affect the quality of life of the elderly. Endothelin-1 is well investigated, is elevated in patients with diabetes, and is related to muscle cellular senescence and fibrosis. However, the mechanism of ET-1 between diabetes and myopathy is still unclear. The aim of this study was to evaluate the prevalence of sarcopenia in the elderly with diabetes and to clarify its relationship with ET-1 molecular biological mechanism, progress as well as changes in muscle and fat.. We recruited 157 type 2 diabetes patients over 55 years old and investigated the prevalence of sarcopenia in diabetes patients and examined the association of ET-1 alterations with HbA1c, creatinine, or AMS/ht2. Next, sought to determine how ET-1 regulates inflammation in muscle cells by western blot and qPCR assay. Using XF Seahorse Technology, we directly quantified mitochondrial bioenergetics in 3T3-L1 cells.. ET-1 was positively correlated with HbA1c, creatinine levels, and duration of disease, and negatively correlated with AMS/ht2. We found that ET-1 dose-dependently induces tumor necrosis factor-α (TNF-α) and interleukin (IL)-6β expression through the PI3K/AKT, and NF-κB signaling pathways in C2C12 cells. Also identified that TNF-α, IL-6β, and visfatin releases were found in co-cultured with conditioned medium of ET-1/C2C12 in 3T3-L1 cells. ET-1 also reduces the energy metabolism of fat and induces micro-environment inflammation which causes myopathy. ET-1 also suppresses miR-let-7g-5p expression in myocytes and adipocytes.. We describe a new mechanism of ET-1 triggering chronic inflammation in patients with hyperglycemia.

Topics: Aged; Creatinine; Diabetes Mellitus, Type 2; Endothelin-1; Glycated Hemoglobin; Humans; Inflammation; MicroRNAs; Muscular Diseases; Phosphatidylinositol 3-Kinases; Quality of Life; Sarcopenia; Tumor Necrosis Factor-alpha

Endothelial dysfunction, with increased endothelin-1 (ET-1) synthesis, and sarcopenia, characterized by the loss of muscular mass and strength, are two aging-related conditions. However, a relationship between them has not been already established. The aim of this study was to determine whether ET-1 induces senescence and fibrosis in cultured murine myoblasts, which could be involved in the development of sarcopenia related to aging. For this purpose, myoblasts were incubated with ET-1 to assess cellular senescence, analyzed by senescence associated β-galactosidase activity and p16 expression; and fibrosis, assessed by fibronectin expression. ET-1 induced myoblast senescence and fibrosis through ET

Topics: Aging; Animals; Antioxidants; Cellular Senescence; Disease Models, Animal; Endothelin-1; Fibrosis; Humans; Male; Mice; Muscle Strength; Muscle, Skeletal; Myoblasts; Reactive Oxygen Species; Receptor, Endothelin A; Sarcopenia