机构:[1]Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, 1 Fuhua Road, Futian District, Shenzhen 518033, Guangdong, China深圳市康宁医院深圳市中医院深圳医学信息中心[2]Department of Critical Care Medicine, Shantou Hospital of Traditional Chinese Medicine, Shantou, China[3]Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, 1 Fuhua Road, Futian District, Shenzhen 518033, Guangdong, China.深圳市康宁医院深圳市中医院深圳医学信息中心
Diabetes-related muscle wasting is one of the devastating complications of diabetes, which is associated with muscle autophagy due to insulin-mediated glucose starvation. However, treatment for diabetes-related muscle wasting is limited. Our previous study already found that niclosamide ethanolamine salt has the therapeutic effects on insulin deficiency of type 1 diabetes mice and muscle wasting induced by doxorubicin. Therefore, we aim to investigate the therapeutic effects of niclosamide ethanolamine salt on diabetes-induced muscle wasting and to explore whether the mechanism is associated with muscle autophagy.Type 1 diabetes mice were induced by intraperitoneal injection of streptozotocin, then were fed with regular diet supplemented with 10 g/kg niclosamide ethanolamine salt. The whole experiment lasted for 8 weeks. At the end of the study, grip strength, weights of tibialis anterior, gastrocnemius, soleus, and extensor digitorum longus muscle were measured. Tibialis anterior muscles stained with PAS were used for evaluating the fiber cross sectional area. Immunofluorescence analysis of myosin heavy chain expression in extensor digitorum longus and soleus muscle was used for determining the composition of the muscle fiber type. Electronic microscopy was applied to observe the autophagy in the atrophied muscle. Serum insulin levels and fasting blood glucose were also measured. Tissues of gastrocnemius muscle were used for detecting the expression of the proteins related to autophagy.In this study, we found that niclosamide ethanolamine salt could ameliorate muscle atrophy in the type 1 diabetes mice as well, such as enhancing the declined grip strength, improving limb weight and increasing the numbers of glycolytic muscle fiber. Electron microscopy also confirmed that there did exist abundant autophagic vacuoles in the atrophied muscle of the type 1 diabetes mice. Specifically, niclosamide ethanolamine salt could reduce the over expression of autophagy-related proteins, including p-AMPK (Thr172), FoxO3a, p-ULK1 (Ser555), LC3B II, and p-p38 in gastrocnemius muscle of the type 1 diabetes mice.Niclosamide ethanolamine salt could ameliorate muscle wasting. The mechanisms underlying might be associated with inhibition of muscle autophagy.
基金:
National Natural Science
Foundation of China (81673794,82004156), Shenzhen Science and
Technology Project (JCYJ20190812183603627), and the Sanming Project of
Medicine in Shenzhen (SZSM201512040).
第一作者机构:[1]Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, 1 Fuhua Road, Futian District, Shenzhen 518033, Guangdong, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Cai Yuchun,Zhan Hongyue,Weng Wenci,et al.Niclosamide ethanolamine ameliorates diabetes-related muscle wasting by inhibiting autophagy.[J].SKELETAL MUSCLE.2021,11(1):doi:10.1186/s13395-021-00272-7.
APA:
Cai Yuchun,Zhan Hongyue,Weng Wenci,Wang Yao,Han Pengxun...&Sun Huili.(2021).Niclosamide ethanolamine ameliorates diabetes-related muscle wasting by inhibiting autophagy..SKELETAL MUSCLE,11,(1)
MLA:
Cai Yuchun,et al."Niclosamide ethanolamine ameliorates diabetes-related muscle wasting by inhibiting autophagy.".SKELETAL MUSCLE 11..1(2021)