Effects of a rhizome aqueous extract of Dioscorea batatas and its bioactive compound, allantoin in high fat diet and streptozotocin-induced diabetic mice and the regulation of liver, pancreas and skeletal muscle dysfunction

Diabetes mellitus is a systemic metabolic disorder associated with mitochondrial dysfunction, with mitochondrial permeability transition (MPT) pore opening being recognized as one of its pathogenic mechanisms. Alisporivir has been recently identified as a non-immunosuppressive analogue of the MPT pore blocker cyclosporin A and has broad therapeutic potential. The purpose of the present work was to study the effect of alisporivir (2.5 mg/kg/day i.p.) on the ultrastructure and functions of the skeletal muscle mitochondria of mice with diabetes mellitus induced by a high-fat diet combined with streptozotocin injections. The glucose tolerance tests indicated that alisporivir increased the rate of glucose utilization in diabetic mice. An electron microscopy analysis showed that alisporivir prevented diabetes-induced changes in the ultrastructure and content of the mitochondria in myocytes. In diabetes, the ADP-stimulated respiration, respiratory control, and ADP/O ratios and the level of ATP synthase in the mitochondria decreased, whereas alisporivir treatment restored these indicators. Alisporivir eliminated diabetes-induced increases in mitochondrial lipid peroxidation products. Diabetic mice showed decreased mRNA levels of Atp5f1a, Ant1, and Ppif and increased levels of Ant2 in the skeletal muscles. The skeletal muscle mitochondria of diabetic animals were sensitized to the MPT pore opening. Alisporivir normalized the expression level of Ant2 and mitochondrial susceptibility to the MPT pore opening. In parallel, the levels of Mfn2 and Drp1 also returned to control values, suggesting a normalization of mitochondrial dynamics. These findings suggest that the targeting of the MPT pore opening by alisporivir is a therapeutic approach to prevent the development of mitochondrial dysfunction and associated oxidative stress in the skeletal muscles in diabetes.

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Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmu065 ◽

2014 ◽

Vol 46 (9) ◽

pp. 738-748 ◽

Cited By ~ 30

Author(s):

X. Li ◽

Z. Xu ◽

Z. Jiang ◽

L. Sun ◽

J. Ji ◽

...

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Biogenesis ◽

High Fat Diet ◽

Hypoglycemic Effect ◽

Diabetic Mice ◽

High Fat

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Trimetazidine and exercise provide comparable improvements to high fat diet-induced muscle dysfunction through enhancement of mitochondrial quality control

Scientific Reports ◽

10.1038/s41598-021-98771-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenliang Zhang ◽

Baiyang You ◽

Dake Qi ◽

Ling Qiu ◽

Jeffrey W. Ripley-Gonzalez ◽

...

Keyword(s):

Skeletal Muscle ◽

Quality Control ◽

Mitochondrial Dysfunction ◽

Muscle Atrophy ◽

High Fat Diet ◽

C2c12 Cells ◽

Muscle Dysfunction ◽

High Fat ◽

Mitochondrial Quality Control ◽

Mitochondrial Functions

AbstractObesity induces skeletal muscle dysfunction. The pathogenesis of which appears to substantially involve mitochondrial dysfunction, arising from impaired quality control. Exercise is a major therapeutic strategy against muscle dysfunction. Trimetazidine, a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, the effects of Trimetazidine on regulating skeletal muscle function are largely unknown. Our present study used cell culture and obese mice models to test a novel hypothesis that Trimetazidine could improve muscle atrophy with similar results to exercise. In C2C12 cells, high palmitic acid-induced atrophy and mitochondrial dysfunction, which could be reversed by the treatment of Trimetazidine. In our animal models, with high-fat diet-induced obesity associated with skeletal muscle atrophy, Trimetazidine prevented muscle dysfunction, corrected metabolic abnormalities, and improved mitochondrial quality control and mitochondrial functions similarly to exercise. Thus, our study suggests that Trimetazidine successfully mimics exercise to enhance mitochondrial quality control leading to improved high-fat diet-induced muscle dysfunction.

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Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

Nutrients ◽

10.3390/nu12010220 ◽

2020 ◽

Vol 12 (1) ◽

pp. 220 ◽

Cited By ~ 4

Author(s):

Qichen Yuan ◽

Biyuan Zhan ◽

Rui Chang ◽

Min Du ◽

Xueying Mao

Keyword(s):

Skeletal Muscle ◽

Gut Microbiota ◽

High Fat Diet ◽

Glucose Transporter ◽

Glycogen Synthase ◽

Fasting Blood Glucose ◽

Diabetic Mice ◽

High Fat ◽

Antidiabetic Effect ◽

Glucose Levels

This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.

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Effects of Rhizome Extract of Dioscorea Batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

10.20944/preprints201806.0398.v1 ◽

2018 ◽

Author(s):

Jun Nan Ma ◽

Seok Yong Kang ◽

Jong Hun Park ◽

Yong-Ki Park ◽

Hyo Won Jung

Keyword(s):

Skeletal Muscle ◽

Glucose Uptake ◽

Mitochondrial Biogenesis ◽

Glucose Consumption ◽

Bioactive Compound ◽

Myoblast Differentiation ◽

C2c12 Myotubes ◽

Glucose Levels ◽

Skeletal Muscle Dysfunction ◽

Dioscorea Batatas

The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese Yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and the extract was analyzed by HPLC. The expression of C2C12 myotubes differentiation and mitochondrial biogenesis regulators were determined by reverse transcriptase (RT)-PCR or Western blot. The glucose levels and total ATP contents were determined by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased of MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of mitochondrial biogenesis regulating proteins, PGC1?, Sirt-1, NRF-1, and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased the glucose uptake levels and the ATP contents. Finally, HPLC analysis revealed that the yam extract contained 1.53% of allantoin. Yam extract and allantoin, stimulated myoblast differentiation into myotubes and increased energy production through upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent the skeletal muscle dysfunction through stimulation of energy metabolism.

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The Treatment of Rhodiola Mimics Exercise to Resist High-Fat Diet-Induced Muscle Dysfunction via Sirtuin1-Dependent Mechanisms

Frontiers in Pharmacology ◽

10.3389/fphar.2021.646489 ◽

2021 ◽

Vol 12 ◽

Author(s):

Baiyang You ◽

Yaoshan Dun ◽

Siqian Fu ◽

Dake Qi ◽

Wenliang Zhang ◽

...

Keyword(s):

Quality Control ◽

High Fat Diet ◽

C2c12 Myotubes ◽

Muscle Dysfunction ◽

High Fat ◽

Mitochondrial Quality Control ◽

Skeletal Muscle Dysfunction ◽

Lipid Metabolism Disorders ◽

Sirt1 Inhibitor

Muscle dysfunction is a complication of high-fat diet (HFD)-induced obesity that could be prevented by exercise, but patients did not get enough therapeutic efficacy from exercise due to multiple reasons. To explore alternative or supplementary approaches to prevent or treat muscle dysfunction in individuals with obesity, we investigated the effects of Rhodiola on muscle dysfunction as exercise pills. SIRT1 might suppress atrogenes expression and improve mitochondrial quality control, which could be a therapeutic target stimulated by exercise and Rhodiola, but further mechanisms remain unclear. We verified the lipid metabolism disorders and skeletal muscle dysfunction in HFD feeding mice. Moreover, exercise and Rhodiola were used to intervene mice with a HFD. Our results showed that exercise and Rhodiola prevented muscle atrophy and dysfunction in obese mice and activating the SIRT1 pathway, while atrogenes were suppressed and mitochondrial quality control was improved. EX-527, SIRT1 inhibitor, was used to validate the essential role of SIRT1 in salidroside benefit. Results of cell culture experiment showed that salidroside alleviated high palmitate-induced atrophy and mitochondrial quality control impairments, but these improvements of salidroside were inhibited by EX-527 in C2C12 myotubes. Overall, Rhodiola mimics exercise that activates SIRT1 signaling leading to improvement of HFD-induced muscle dysfunction.

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