scholarly journals Corrigendum to “Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux” [Life Sci. 2020 Oct 1;258:118243]

Life Sciences ◽  
2021 ◽  
pp. 119589
Author(s):  
Zhen Fan ◽  
Jing Wu ◽  
Qiu-nan Chen ◽  
An-kang Lyu ◽  
Jin-liang Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Autophagic Flux

Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux

Life Sciences ◽  
2020 ◽  
Vol 258 ◽  
pp. 118243 ◽  
Author(s):  
Zhen Fan ◽  
Jing Wu ◽  
Qiu-nan Chen ◽  
An-kang Lyu ◽  
Jin-liang Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Autophagic Flux

scholarly journals An endocrine-hepato-muscular metabolic cycle links skeletal muscle atrophy and hyperglycemia in type 2 diabetes

2020 ◽  
Author(s):  
Jürgen G. Okun ◽  
Patricia M. Rusu ◽  
Andrea Y. Chan ◽  
Yann W. Yap ◽  
Thomas Sharkie ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Ex Vivo ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Atrophy ◽  
Diabetic Mice ◽  
Metabolic Cycle

AbstractBoth obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we uncover dysregulated systemic alanine metabolism and hyper-expression of the alanine transaminases (ALT) in the liver of obese/diabetic mice and humans. Hepatocyte-selective silencing of both ALT enzymes revealed a clear role in systemic alanine clearance which related to glycemic control. In obese/diabetic mice, not only did silencing both ALT enzymes retard hyperglycemia, but also reversed skeletal muscle atrophy. This was due to a rescue of depressed skeletal muscle protein synthesis, with a liver-skeletal muscle amino acid metabolic crosstalk exemplified by ex vivo experiments. Mechanistically, chronic liver glucocorticoid and glucagon signaling driven liver alanine catabolism promoted hyperglycemia and skeletal muscle wasting. Taken together, here we reveal an endocrine-hepato-muscular metabolic cycle linking hyperglycemia and skeletal muscle atrophy in type 2 diabetes.

Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes

2021 ◽  
Vol 3 (3) ◽  
pp. 394-409
Author(s):  
Jürgen G. Okun ◽  
Patricia M. Rusu ◽  
Andrea Y. Chan ◽  
Yuqin Wu ◽  
Yann W. Yap ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy

scholarly journals MicroRNA-193b impairs muscle growth in mouse models of type 2 diabetes by targeting the PDK1/Akt signalling pathway

Diabetologia ◽  
2021 ◽  
Author(s):  
Shu Yang ◽  
Guangyan Yang ◽  
Han Wu ◽  
Lin Kang ◽  
Jiaqing Xiang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Fasting Blood Glucose ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
Skeletal Muscle Atrophy ◽  
Muscle Loss ◽  
Functional Studies

Abstract Aims/hypothesis Type 2 diabetes is associated with a reduction in skeletal muscle mass; however, how the progression of sarcopenia is induced and regulated remains largely unknown. We aimed to find out whether a specific microRNA (miR) may contribute to skeletal muscle atrophy in type 2 diabetes. Methods Adeno-associated virus (AAV)-mediated skeletal muscle miR-193b overexpression in C57BLKS/J mice, and skeletal muscle miR-193b deficiency in db/db mice were used to explore the function of miR-193b in muscle loss. In C57BL/6 J mice, tibialis anterior-specific deletion of 3-phosphoinositide-dependent protein kinase-1 (PDK1), mediated by in situ AAV injection, was used to confirm whether miR-193b regulates muscle growth through PDK1. Serum miR-193b levels were also analysed in healthy individuals (n = 20) and those with type 2 diabetes (n = 20), and correlations of miR-193b levels with HbA1c, fasting blood glucose (FBG), body composition, triacylglycerols and C-peptide were assessed. Results In this study, we found that serum miR-193b levels increased in individuals with type 2 diabetes and negatively correlated with muscle mass in these participants. Functional studies further showed that AAV-mediated overexpression of miR-193b induced muscle loss and dysfunction in healthy mice. In contrast, suppression of miR-193b attenuated muscle loss and dysfunction in db/db mice. Mechanistic analysis revealed that miR-193b could target Pdk1 expression to inactivate the Akt/mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway, thereby inhibiting protein synthesis. Therefore, knockdown of PDK1 in healthy mice blocked miR-193b-induced inactivation of the Akt/mTOR/S6K pathway and impairment of muscle growth. Conclusions/interpretation Our results identified a previously unrecognised role of miR-193b in muscle function and mass that could be a potential therapeutic target for treating sarcopenia. Graphical abstract

scholarly journals miR-23b-3p acts as a counter-response against skeletal muscle atrophy

2020 ◽  
Vol 244 (3) ◽  
pp. 535-547 ◽  
Author(s):  
Takuro Okamura ◽  
Yoshitaka Hashimoto ◽  
Takafumi Osaka ◽  
Takafumi Senmaru ◽  
Takuya Fukuda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Protein Synthesis ◽  
Glucose Uptake ◽  
Myosin Heavy Chain ◽  
Muscle Atrophy ◽  
Heavy Chain ◽  
Muscle Protein ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotube

To investigate the role of microRNA (miRNA) in muscle atrophy, we performed microarray analysis of miRNA expression in skeletal muscles of Sham, orchiectomized (ORX) mice, and ORX mice treated with androgen and identified that the expression of miR-23b-3p in ORX mice was significantly higher than that in Sham mice (P = 0.007); however, miR-23b-3p expression in ORX mice treated with androgen was lower (P = 0.001). We also investigated the mechanism by which overexpression or knockdown of miR-23b-3p influences the expression of myosin heavy chain, muscle protein synthesis, ATP activity, and glucose uptake in C2C12 myotube cells. Moreover, we examined the serum miR-23b-3p levels among male subjects with type 2 diabetes and whether the serum miR-23b-3p levels could be a biomarker for muscle atrophy. The overexpression of miR-23b-3p in C2C12 myotube cells significantly upregulated the expression of myosin heavy chain, protein synthesis, ATP activity, and glucose uptake. Reporter assays raised a possible direct post-transcriptional regulation involving miR-23b-3p and the 3′-UTR of PTEN mRNA. Among subjects with type 2 diabetes, serum miR-23b-3p levels in the subjects with decreased muscle mass were significantly higher compared to the levels in the subjects without. Our results indicate that miR-23b-3p downregulates the expression of PTEN in myotube cells and induces the growth of myosin heavy chain. In addition, the serum level of miR-23b-3p can be used as a diagnostic marker for muscle atrophy.

scholarly journals Angiotensin-(1-7) Prevents Lipopolysaccharide-Induced Autophagy via the Mas Receptor in Skeletal Muscle

2020 ◽  
Vol 21 (24) ◽  
pp. 9344
Author(s):  
Juan Carlos Rivera ◽  
Johanna Abrigo ◽  
Franco Tacchi ◽  
Felipe Simon ◽  
Enrique Brandan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
B Cell Lymphoma ◽  
Mapk Signaling ◽  
C2c12 Cells ◽  
Skeletal Muscle Atrophy ◽  
Autophagic Flux ◽  
Mrna Levels ◽  
Mas Receptor ◽  
The Impact

Skeletal muscle atrophy, which occurs in lipopolysaccharide (LPS)-induced sepsis, causes a severe muscle function reduction. The increased autophagy contributes to sepsis-induced skeletal muscle atrophy in a model of LPS injection, increasing LC3II/LC3I ratio, autophagy flux, and autophagosomes. Angiotensin-(1-7) (Ang-(1-7)) has anti-atrophic effects via the Mas receptor in skeletal muscle. However, the impact of Ang-(1-7) on LPS-induced autophagy is unknown. In this study, we determined the effect of Ang-(1-7) on sepsis-induced muscle autophagy. C57BL6 wild-type (WT) mice and mice lacking the Mas receptor (KO Mas) were injected with LPS together with the systemic administration of Ang-(1-7) to determine autophagy in skeletal muscle. We also evaluated autophagy and p38 and c-Jun N-terminal kinase (JNK)activation. Our results show that Ang-(1-7) prevents LPS-induced autophagy in the diaphragm, tibialis anterior, and gastrocnemius of WT mice, which is demonstrated by a decrease in the LC3II/LC3I ratio and mRNA levels of lc3b and ctsl. This effect was lost in KO Mas mice, suggesting the role of the Mas receptor. The results in C2C12 cells show that Ang-(1-7) reduces several LPS-dependent effects, such as autophagy (LC3II/LC3I ratio, autophagic flux, and autophagosomes), activation of p38 and JNK, B-cell lymphoma-2 (BCL2) phosphorylation, and disassembly of the Beclin1/BCL2 complex. In conclusion, Ang-(1-7)/Mas receptor reduces LPS-induced autophagy in skeletal muscle. In vitro assays indicate that Ang-(1-7) prevents LPS-induced autophagy and modifies the MAPK signaling and the disassembly of a complex involved at the beginning of autophagy.

scholarly journals Resistance Training Alleviates Skeletal Muscle Atrophy in Rats Exposed to Hypoxia by inhibiting Autophagy Mediated by Acetyl-FoxO1

2020 ◽  
Author(s):  
Pengyu FU ◽  
KONG Zhaowei ◽  
GONG Lijing ◽  
Hans-Christer Holmberg ◽  
LI Yanchun ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Muscle Atrophy ◽  
Muscular Atrophy ◽  
Training Group ◽  
Skeletal Muscle Atrophy ◽  
Control Group ◽  
Autophagic Flux ◽  
Sequestosome 1 ◽  
Control Group Group

Abstract Background: Skeletal muscle atrophy induced by hypoxia could affect the physical fitness and training effect of the athletes in the rapid altitude, and also affect the production and life of the general public. Resistance training in a hypoxic environment could effectively alleviate the occurrence of muscular atrophy. Whether autophagy lysosomal pathway, as an important proteolysis pathway, is involved in this process, and whether FoxO1, the key gene of atrophy, plays a role by regulating autophagy is unclear. Methods: Male Sprague-Dawley (SD) rats were randomly divided into normoxic control group (group C), normoxic resistance-training group (group R), hypoxic control group (group H), and hypoxic resistance-training group (group HR). The H and HR groups were exposed to 12.4% oxygen for four weeks. The R and HR groups underwent incremental loaded training by climbing a ladder every other day for four weeks. Results: Compared to parameters in group H, resistance training increased lean body mass (LBM) and wet weight and decreased the expression of atrogin1 of the extensor digitorum longus (EDL) after four weeks ( P <0.05). Resistance training decreased the levels of FoxO1 and Ac-FoxO1 and the extent of their localization in the nucleus and cytoplasm, respectively ( P <0.05), as well as the LC3II/LC3I ratio, the integrated optical density (IOD) of LC3 and the levels of autophagy-related gene 7 (Atg7), and elevated the levels of sequestosome 1 (SQSTM1/p62) ( P <0.05). Most differentially expressed autophagy-related genes (ATGs) interacted with FoxO1, and the functions of these ATGs were mainly enriched in the early autophagy phase. Conclusions: Our findings demonstrate that resistance training lowers the levels of both nuclear FoxO1 and cytoplasmic Ac-FoxO1, as well as reduced autophagic flux in the EDL of rats exposed to hypoxia.

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