Campanumoea javanica Bl. activates the PI3K/AKT/mTOR signaling pathway and reduces sarcopenia in a T2DM rat model
Xiangyu Zuo, Rongfei Yao, Linyi Zhao, Yinjiang Zhang, Binan Lu, Zongran Pang
Campanumoea javanica Bl. activates the PI3K/AKT/mTOR signaling pathway and reduces sarcopenia in a T2DM rat model
Objective: Sarcopenia causes loss of skeletal muscle and function, thus seriously affecting the physical function and quality of life in the elderly. This article discusses the specific molecular mechanism and ameliorating effects of Tudangshen (TDS) on sarcopenia in elderly rats with type 2 diabetes mellitus (T2DM).
Methods: Elderly Sprague-Dawley (SD) rats were randomly selected and fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish T2DM model. The model rats were stratified and randomly divided into model group, metformin group, TDS high-dose group, TDS medium-dose group, and TDS low-dose group according to blood glucose combined with body weight, and the same batch of old SD rats were set as normal control group. The effects of TDS in an elderly T2DM sarcopenia rat model were evaluated by observing body positions of the rats, analyzing blood biochemistry, testing exercise capacity, and pathologically staining sectioned gastrocnemius muscle tissues. The molecular mechanisms of the effects were analyzed using quantitative real-time polymerase chain reaction and western blotting.
Results: TDS has no statistically significant effect on blood glucose, insulin and glycosylated serum protein in aged rats with T2DM, but it can reduce levels of glycosylated serum protein, total cholesterol, triglycerides, and low-density lipoprotein; it improves pathological changes in rat gastrocnemius muscle tissues, and increases muscle cell activity in elderly rats with T2DM and sarcopenia. TDS also promoted the upregulation of the expression of mammalian target of rapamycin (mTOR)/protein kinase B (PKB/Akt)/phosphatidylinositol 3-kinase (PI3K)/ribosomal protein S6 kinase/eukaryotic initiation factor 4E binding rotein1 mRNA in rats and triggered an increase in corresponding protein levels.
Conclusions: TDS alleviated muscle decline in elderly rats with T2DM by activating the PI3K/AKT/mTOR signaling pathway and regulating the synthesis of corresponding proteins.
Campanumoea javanica Bl. / Sarcopenia / Tudangshen / Type 2 diabetes mellitus / PI3K/Akt/mTOR
[[1]] |
Ali HZ, Anwar M, Elizabeth M, et al.Diabetes: a fast evolving epidemic. Kuwait Med J 2015;47(4):291-301.
|
[[2]] |
Sinclair A, Saeedi P, Kaundal A, et al.Diabetes and global ageing among 65-99-year-old adults: Findings from the International Diabetes Federation Diabetes Atlas. 9th edition. Diabetes Research and Clinical Practice 2020;162:108078.
|
[[3]] |
Roden M, Shulman GI.The integrative biology of type 2 diabetes. Nature 2019;576(7785):51-60. doi:10.1038/s41586-019-1797-8.
|
[[4]] |
Davison GW, Irwin RE, Walsh CP.The metabolic-epigenetic nexus in type 2 diabetes mellitus. Free Radic Biol Med 2021;170:194-206.
|
[[5]] |
Wilkinson DJ, Piasecki M, Atherton PJ.The age-related loss of skeletal muscle mass and function: measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans. Ageing Res Rev 2018;47:123-132.
|
[[6]] |
Ekici R, Erden A, Güven SC, et al.Prevalence of sarcopenia and clinical implications in newly diagnosed rheumatoid arthritis patients. Nutrition 2021;90:111353.
|
[[7]] |
Seol A, Kim SI, Song YS.Sarcopenia: clinical implications in ovarian cancer, diagnosis, etiology, and management. Sports Med Health Sci 2020;2(4):202-210.
|
[[8]] |
Shafiee G, Keshtkar A, Soltani A, et al.Prevalence of sarcopenia in the world: a systematic review and meta-analysis of general population studies. J Diabetes Metab Disord 2017;16:21.
|
[[9]] |
Sugimoto K, Tabara Y, Ikegami H, et al.Hyperglycemia in nonobese patients with type 2 diabetes is associated with low muscle mass: the multicenter study for clarifying evidence for sarcopenia in patients with diabetes mellitus. J Diabetes Investig 2019;10(6):1471-1479.
|
[[10]] |
Umegaki H.Sarcopenia and diabetes: hyperglycemia is a risk factor for age-associated muscle mass and functional reduction. J Diabetes Investig 2015;6(6):623-624.
|
[[11]] |
Morley JE.Sarcopenia in the elderly. Fam Pract 2012;29(Suppl 1): i44-i48.
|
[[12]] |
Leenders M, Verdijk LB, van der Hoeven L, et al. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 2013;14(8):585-592.
|
[[13]] |
Kim TN, Park MS, Yang SJ, et al.Prevalence and determinant factors of sarcopenia in patients with type 2 diabetes: the Korean Sarcopenic Obesity Study (KSOS). Diabetes Care 2010;33(7):1497-1499.
|
[[14]] |
Deng J, Yang J, Wu L-F, et al.Structural characterization and neurotrophic activity study of a polysaccharide isolated from Campanumoea javanica. J Carbohydr Chem 2015;34(4):183-195.
|
[[15]] |
Wang Y.Color Atlas of Chinese Miao Drugs. Guiyang: Guizhou Science and Technology Press; 2002. 40.
|
[[16]] |
Wang T, Feng X, Zhou J, et al.Type 2 diabetes mellitus is associated with increased risks of sarcopenia and pre-sarcopenia in Chinese elderly. Sci Rep 2016;6:38937. doi:10.1038/srep38937.
|
[[17]] |
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017;169(2):361-371.
|
[[18]] |
Yin X, Xu Z, Zhang Z, et al.Association of PI3K/AKT/mTOR pathway genetic variants with type 2 diabetes mellitus in Chinese. Diabetes Res Clin Pract 2017;128:127-135.
|
[[19]] |
Palmer AJ, Chung MY, List EO, et al.Age-related changes in body composition of bovine growth hormone transgenic mice. Endocrinology 2009;150(3):1353-1360.
|
[[20]] |
Tunc-Ata M, Altintas F, Senol H, et al.Ileal interposition improves metabolic syndrome parameters in a rat model of metabolic syndrome induced by monosodium glutamate. Life Sci 2021;266: 118846.
|
[[21]] |
Hahn P, Song Y, Ying GS, et al.Age-dependent and gender-specific changes in mouse tissue iron by strain. Exp Gerontol 2009;44(9):594-600.
|
[[22]] |
Li H, Wang R, Wang L, et al.Bovine milk fat globule epidermal growth factor VIII activates PI3K/Akt signaling pathway and attenuates sarcopenia in rat model induced by D-galactose. Food Biosci 2021;40.
|
[[23]] |
Rhoads TW, Clark JP, Gustafson GE, et al. Molecular and functional networks linked to sarcopenia prevention by caloric restriction in rhesus monkeys. Cell Syst 2020;10(2):156-168. e5.
|
[[24]] |
Anwar M, Mallick S, Paliwal D, et al.Impact of physical activity on mitochondrial enzymes, muscle stem cell and anti-oxidant protein Sestrins in sarcopenic mice. Exp Gerontol 2021;150:111358.
|
[[25]] |
Chatterjee S, Davies MJ, Tarigopula G.Pharmacological control of blood sugar. Anaesth Intensive Care Med 2017;18(10):532-534.
|
[[26]] |
Wang Z, Zhou J, Lu M, et al.Therapy of empagliflozin plus metformin on T2DM mice shows no higher amelioration for glucose and lipid metabolism than empagliflozin monotherapy. Life Sci 2019;232:116622.
|
[[27]] |
Neri-Numa IA, Cazarin CBB, Ruiz ALTG, et al.Targeting flavonoids on modulation of metabolic syndrome. J Funct Foods 2020;73:104132.
|
[[28]] |
Kang HT, Yoon JH, Kim JY, et al.The association between the ratio of triglyceride to HDL-C and insulin resistance according to waist circumference in a rural Korean population. Nutr Metab Cardiovasc Dis 2012;22(12):1054-1060.
|
[[29]] |
Hadaegh F, Khalili D, Ghasemi A, et al.Triglyceride/HDLcholesterol ratio is an independent predictor for coronary heart disease in a population of Iranian men. Nutr Metab Cardiovasc Dis 2009;19(6):401-408.
|
[[30]] |
He J, He S, Liu K, et al.The TG/HDL-C ratio might be a surrogate for insulin resistance in Chinese nonobese women. Int J Endocrinol 2014;2014:105168.
|
[[31]] |
Chung TH, Kwon YJ, Shim JY, et al.Association between serum triglyceride to high-density lipoprotein cholesterol ratio and sarcopenia in elderly Korean males: the Korean National Health and Nutrition Examination Survey. Clin Chim Acta 2016;463: 165-168.
|
[[32]] |
Kim JS, Kang HT, Shim JY, et al.The association between the triglyceride to high-density lipoprotein cholesterol ratio with insulin resistance (HOMA-IR) in the general Korean population: based on the National Health and Nutrition Examination Survey in 2007-2009. Diabetes Res Clin Pract 2012;97(1):132-138.
|
[[33]] |
Angulo J, El Assar M, Rodriguez-Manas L.Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. Mol Aspects Med 2016;50:1-32.
|
[[34]] |
Sarodnik C, Bours SPG, Schaper NC, et al.The risks of sarcopenia, falls and fractures in patients with type 2 diabetes mellitus. Maturitas 2018;109:70-77.
|
[[35]] |
Cola SD, Lattanzi B, D'ambrosio D, et al.FRI-428-prevalence and impact of sarcopenia in non-cirrhotic portal hypertension. J Hepatol 2019;70(1):e582.
|
[[36]] |
Aibar-Almazán A, Martínez-Amat A, Cruz-Díaz D, et al.Sarcopenia and sarcopenic obesity in Spanish community-dwelling middle-aged and older women: association with balance confidence, fear of falling and fall risk. Maturitas 2018;107:26-32.
|
[[37]] |
Dent E, Morley JE, Cruz-Jentoft AJ, et al.International Clinical Practice Guidelines for Sarcopenia (ICFSR): screening, diagnosis and management. J Nutr Health Aging 2018;22(10):1148-1161.
|
[[38]] |
Scott D, Johansson J, Gandham A, et al.Associations of accelerometer-determined physical activity and sedentary behavior with sarcopenia and incident falls over 12 months in communitydwelling Swedish older adults. J Sport Health Sci 2021;10(5):577-584.
|
[[39]] |
Sparling PB, Howard BJ, Dunstan DW, et al.Recommendations for physical activity in older adults. BMJ 2015;350:h100.
|
[[40]] |
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017;168(6):960-976.
|
[[41]] |
Qin X, Jiang B, Zhang Y.4E-BP1, a multifactor regulated multifunctional protein. Cell Cycle 2016;15(6):781-786.
|
[[42]] |
Pizzini A, Bacher H, Aichner M, et al.High expression of mTOR signaling in granulomatous lesions is not predictive for the clinical course of sarcoidosis. Respir Med 2021;177:106294.
|
[[43]] |
Xiao Q, Yu H, Zhu X.The associations of hub gene polymorphisms in PI3K/AKT/mTOR pathway and Schistosomiasis japonica infection and hepatic fibrosis. Infect Genet Evol 2020; 85:104423.
|
/
〈 | 〉 |