scholarly journals AKT2 regulates development and metabolic homeostasis via AMPK-depedent pathway in skeletal muscle

2020 ◽  
Vol 134 (17) ◽  
pp. 2381-2398
Author(s):  
Miao Chen ◽  
Caoyu Ji ◽  
Qingchen Yang ◽  
Shuya Gao ◽  
Yue Peng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
The Body ◽  
Glucose Disposal ◽  
Ampk Activation ◽  
Skeletal Muscle Development ◽  
Ampk Signaling ◽  
Expression Of Genes ◽  
Total Glucose ◽  
Amp Activated Protein Kinase

Abstract Skeletal muscle is responsible for the majority of glucose disposal in the body. Insulin resistance in the skeletal muscle accounts for 85–90% of the impairment of total glucose disposal in patients with type 2 diabetes (T2D). However, the mechanism remains controversial. The present study aims to investigate whether AKT2 deficiency causes deficits in skeletal muscle development and metabolism, we analyzed the expression of molecules related to skeletal muscle development, glucose uptake and metabolism in mice of 3- and 8-months old. We found that AMP-activated protein kinase (AMPK) phosphorylation and myocyte enhancer factor 2 (MEF2) A (MEF2A) expression were down-regulated in AKT2 knockout (KO) mice, which can be inverted by AMPK activation. We also observed reduced mitochondrial DNA (mtDNA) abundance and reduced expression of genes involved in mitochondrial biogenesis in the skeletal muscle of AKT2 KO mice, which was prevented by AMPK activation. Moreover, AKT2 KO mice exhibited impaired AMPK signaling in response to insulin stimulation compared with WT mice. Our study establishes a new and important function of AKT2 in regulating skeletal muscle development and glucose metabolism via AMPK-dependent signaling.

scholarly journals AKT2 deficiency causes sarcopenia and metabolic disorder of skeletal muscle

2019 ◽  
Author(s):  
Miao Chen ◽  
Caoyu Ji ◽  
Fei Xiao ◽  
Dandan Chen ◽  
Shuya Gao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mitochondrial Biogenesis ◽  
Muscle Development ◽  
The Body ◽  
Glucose Disposal ◽  
Ampk Activation ◽  
Skeletal Muscle Development ◽  
Independent Manner

AbstractSkeletal muscle is responsible for the majority of glucose disposal in the body. Insulin resistance in the skeletal muscle accounts for 85-90% of the impairment of total body glucose disposal in patients with tye 2 diabetes (T2D). However, the mechanism remains controversial. AKT2 is a protein kinase performing important functions in the regulation of glucose metabolism. We observed that mice deficient for AKT2 (AKT2 KO) exhibited decreased body weight and lean mass and showed impaired glucose tolerance, compared to their age- and gender-matched wild type mice (WT). Therefore, to test whether AKT2 deficiency causes deficits in skeletal muscle development and metabolism, we analyzed the expression of molecules related to skeletal muscle development, glucose uptake and metabolism in young (3 months) and old (8 months) mice. We found that AMPK phosphorylation and MEF2A expression were downregulated in young AKT2 KO mice, and this downregulation was inverted by AMPK activation. We also observed reduced mtDNA abundance and reduced expression of genes involved in mitochondrial biogenesis in the skeletal muscle of adult AKT2 KO mice, which was prevented by AMPK activation. However, GLUT4 expression was regulated by AKT2 in an AMPK-independent manner in skeletal muscle. During high-fat-diet (HFD)-induced obesity, AKT2 KO mice exhibited increased insulin resistance compared to WT mice. Our study establishes a new and important function of AKT2 in regulating glucose uptake and AMPK-dependent development and mitochondrial biogenesis in skeletal muscle.

The ABCs of IGF-I isoforms: impact on muscle hypertrophy and implications for repair

2006 ◽  
Vol 31 (6) ◽  
pp. 791-797 ◽  
Author(s):  
Elisabeth R. Barton
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Muscle Development ◽  
Critical Role ◽  
The Body ◽  
Skeletal Muscle Development ◽  
Active Peptides ◽  
Igf I ◽  
Physiological Impact

Insulin-like growth factor I (IGF-I) plays a critical role in the growth and development of many tissues in the body. It is a key regulator of skeletal muscle development, and continues to enhance the ability for muscle to grow and undergo repair throughout life. Although the focus of research has been on the molecular actions and physiological impact of IGF-I, there has also been a growing undercurrent of studies geared toward the characterization of additional potentially active peptides produced by the igf1 gene. Alternative splicing of the gene results in multiple isoforms that retain the identical sequence for mature IGF-I, but also give rise to divergent C-terminal peptides. The peptides might modulate the actions, stability, or bioavailability of IGF-I, or they might have independent activity. These possibilities have gained the attention of the skeletal muscle field, where novel actions of IGF-I could have significant impact on muscle mass, strength, and repair.

Central infusion of leptin does not increase AMPK signaling in skeletal muscle of sheep

2011 ◽  
Vol 300 (2) ◽  
pp. R511-R518 ◽  
Author(s):  
Rhianna C. Laker ◽  
Belinda A. Henry ◽  
Glenn D. Wadley ◽  
Iain J. Clarke ◽  
Benedict J. Canny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Food Intake ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Ampk Activation ◽  
Plasma Epinephrine ◽  
Ampk Signaling ◽  
Artificial Cerebrospinal Fluid ◽  
Epinephrine Concentration

In sheep, central leptin infusion reduces food intake and increases energy expenditure in adipose tissue and skeletal muscle. The mechanisms for these peripheral effects of central leptin in sheep are not known but, on the basis of rodent studies, may involve AMPK. In mice, central leptin acutely increases both skeletal muscle AMPK activation and glucose uptake. Thus, to investigate whether these effects exist in higher-order mammals, ovariectomized Corriedale ewes ( n = 4 per group) received a continuous lateral ventricular infusion (60 μl/h) of either leptin (50 μg/h) or artificial cerebrospinal fluid (aCSF; CON) for 8 days. Tritiated glucose (3-3H-glucose) was infused intravenously for calculation of whole body glucose turnover during both acute (6 h) and chronic (7–8 days) leptin/aCSF infusion. Muscle biopsies were also obtained. Leptin infusion reduced ( P < 0.05) food intake and body weight, and it also increased plasma epinephrine concentration at 6 h and 7 days, suggesting increased sympathetic nerve activity. Despite this, and in contrast to rodent studies, central leptin infusion did not increase skeletal muscle AMPKα Thr172 phosphorylation or ACCβ Ser221 phosphorylation. Surprisingly, the glucose rate of appearance (glucose Ra) and rate of disappearance (glucose Rd) were reduced by both acute and chronic leptin infusion. Direct infusion of the AMPK activator 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) into the femoral artery increased skeletal muscle AMPK phosphorylation. In conclusion, although central leptin infusion in sheep caused the predicted reduction in food intake and increases plasma epinephrine concentration, it had no effect on AMPK activation in skeletal muscle and actually reduced glucose disposal. This suggests that there are species differences in the peripheral responses to central leptin infusion.

scholarly journals RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
De-Li Shi ◽  
Raphaëlle Grifone
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Binding Proteins ◽  
Muscle Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
The Body ◽  
Skeletal Muscle Development ◽  
Myogenic Program

Embryonic myogenesis is a temporally and spatially regulated process that generates skeletal muscle of the trunk and limbs. During this process, mononucleated myoblasts derived from myogenic progenitor cells within the somites undergo proliferation, migration and differentiation to elongate and fuse into multinucleated functional myofibers. Skeletal muscle is the most abundant tissue of the body and has the remarkable ability to self-repair by re-activating the myogenic program in muscle stem cells, known as satellite cells. Post-transcriptional regulation of gene expression mediated by RNA-binding proteins is critically required for muscle development during embryogenesis and for muscle homeostasis in the adult. Differential subcellular localization and activity of RNA-binding proteins orchestrates target gene expression at multiple levels to regulate different steps of myogenesis. Dysfunctions of these post-transcriptional regulators impair muscle development and homeostasis, but also cause defects in motor neurons or the neuromuscular junction, resulting in muscle degeneration and neuromuscular disease. Many RNA-binding proteins, such as members of the muscle blind-like (MBNL) and CUG-BP and ETR-3-like factors (CELF) families, display both overlapping and distinct targets in muscle cells. Thus they function either cooperatively or antagonistically to coordinate myoblast proliferation and differentiation. Evidence is accumulating that the dynamic interplay of their regulatory activity may control the progression of myogenic program as well as stem cell quiescence and activation. Moreover, the role of RNA-binding proteins that regulate post-transcriptional modification in the myogenic program is far less understood as compared with transcription factors involved in myogenic specification and differentiation. Here we review past achievements and recent advances in understanding the functions of RNA-binding proteins during skeletal muscle development, regeneration and disease, with the aim to identify the fundamental questions that are still open for further investigations.

scholarly journals Key Genes Regulating Skeletal Muscle Development and Growth in Farm Animals

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 835
Author(s):  
Mohammadreza Mohammadabadi ◽  
Farhad Bordbar ◽  
Just Jensen ◽  
Min Du ◽  
Wei Guo
Keyword(s):  
Skeletal Muscle ◽  
Candidate Genes ◽  
Meat Quality ◽  
Muscle Development ◽  
Muscle Growth ◽  
Farm Animals ◽  
Meat Production ◽  
Skeletal Muscle Development ◽  
Extrinsic Factors ◽  
Myogenic Regulatory Factor

Farm-animal species play crucial roles in satisfying demands for meat on a global scale, and they are genetically being developed to enhance the efficiency of meat production. In particular, one of the important breeders’ aims is to increase skeletal muscle growth in farm animals. The enhancement of muscle development and growth is crucial to meet consumers’ demands regarding meat quality. Fetal skeletal muscle development involves myogenesis (with myoblast proliferation, differentiation, and fusion), fibrogenesis, and adipogenesis. Typically, myogenesis is regulated by a convoluted network of intrinsic and extrinsic factors monitored by myogenic regulatory factor genes in two or three phases, as well as genes that code for kinases. Marker-assisted selection relies on candidate genes related positively or negatively to muscle development and can be a strong supplement to classical selection strategies in farm animals. This comprehensive review covers important (candidate) genes that regulate muscle development and growth in farm animals (cattle, sheep, chicken, and pig). The identification of these genes is an important step toward the goal of increasing meat yields and improves meat quality.

Plectin regulates Wnt signaling mediated-skeletal muscle development by interacting with Dishevelled-2 and antagonizing autophagy

Gene ◽  
2021 ◽  
Vol 783 ◽  
pp. 145562
Author(s):  
Huadong Yin ◽  
Shunshun Han ◽  
Can Cui ◽  
Yan Wang ◽  
Diyan Li ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wnt Signaling ◽  
Muscle Development ◽  
Skeletal Muscle Development
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