IRS-1 targets TAZ to inhibit adipogenesis of rat bone marrow mesenchymal stem cells through PI3K-Akt and MEK-ERK pathways

Wang, Na; Li, Yukun; Li, Ziyi; Ma, Jianxia; Wu, Xuelun; Pan, Runzhou; Wang, Yan; Gao, Liu; Bao, Xiaoyong; Xue, Peng

doi:10.1016/j.ejphar.2019.01.064

Cited by 21 publications

(20 citation statements)

References 30 publications

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“…Dysregulation of the insulin signaling cascade results in IR [7], which has important consequences on the regulation of glucose and lipid metabolism. The two major pathways of insulin receptor signal transduction are the insulin receptor substrate (IRS)-PI3K-Akt (also known as PKB) pathway and the growth factor receptor-bound protein 2 (Grb2)-son of sevenless homologue 1 (SOS)-Ras-MAPK pathway (also known as the ERK pathway) [8,9].…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

Chen

Fan

Zheng

et al. 2020

Preprint

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Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance. Methods: In the current study, db/m and db/dbmice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

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Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

Chen

Fan

Zheng

et al. 2020

Preprint

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“…A recent in vitro study, however, showed that IRS-1 negatively regulates rodent BMSC adipogenesis as overexpression of IRS-1 decreased the gene expression of adipogenic markers Cebpβ and Pparγ, while IRS-1 deficiency upregulated Cebpβ and Pparγ. The mechanism by which IRS-1 regulates rat BMSC adipogenesis in this study was mediated partially by PI3K-AKT and MEK-ERK pathways [25]. Contrary to IRS-1, IRS-2 positively regulates adipogenesis in human BMSC as Irs-2 expression was induced during adipogenesis, while IRS-2 deficiency repressed adipogenesis and led to downregulation of Cebpα and Pparγ.…”

Section: Insulin Receptor Substances 1 Andmentioning

confidence: 57%

Insulin Signaling in Bone Marrow Adipocytes

Tencerová

Okla

Kassem

2019

Curr Osteoporos Rep

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Purpose of Review The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases. Recent Findings Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. Summary This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.with enhanced insulin sensitivity, glucose uptake, and oxidative phosphorylation. This metabolic phenotype of BMSC in obesity results in increased ROS production, which might lead to creation of senescent bone marrow microenvironment and stem cell exhaustion contributing to bone fragility in metabolic bone diseases Curr Osteoporos Rep (2019) 17:44 -454 6 447

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“…In contrast, the mechanism, by which the initial activation of Akt leads to TAZ activation, is not clear. Although there are several reports that Akt activates TAZ, the underlying molecular mechanism is yet unknown [47,48]. One paper reported that Akt inhibits GSK3β and increases TAZ expression level [47].…”

Section: Plos Onementioning

confidence: 99%

Characterization of a novel compound that promotes myogenesis via Akt and transcriptional co-activator with PDZ-binding motif (TAZ) in mouse C2C12 cells

et al. 2020

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IRS-1 targets TAZ to inhibit adipogenesis of rat bone marrow mesenchymal stem cells through PI3K-Akt and MEK-ERK pathways

Cited by 21 publications

References 30 publications

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

Insulin Signaling in Bone Marrow Adipocytes

Characterization of a novel compound that promotes myogenesis via Akt and transcriptional co-activator with PDZ-binding motif (TAZ) in mouse C2C12 cells

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