Research Paper Volume 14, Issue 8 pp 3633—3651
Endothelin-1-mediated miR-let-7g-5p triggers interlukin-6 and TNF-α to cause myopathy and chronic adipose inflammation in elderly patients with diabetes mellitus
- 1 Department of Family Medicine, Chung-Kang Branch, Cheng Ching Hospital, Taichung, Taiwan
- 2 Center for General Education, Tunghai University, Taiwan
- 3 Bachelor of Science in Senior Wellness and Sport Science, Tunghai University, Taiwan
- 4 Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan
- 5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- 6 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- 7 School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- 8 Division of Traditional Chinese Medical, Sinying Hospital, Tainan, Taiwan
- 9 Senior Life and Innovation Technology Center, Tunghai University, Taiwan
- 10 Life Science Research Center, Tunghai University, Taiwan
Received: February 10, 2022 Accepted: April 13, 2022 Published: April 25, 2022https://doi.org/10.18632/aging.204034
How to Cite
Copyright: © 2022 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: 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.
Methods: 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.
Results: 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.
Conclusion: We describe a new mechanism of ET-1 triggering chronic inflammation in patients with hyperglycemia.