Modulation de la sensibilité à l’insuline par les adapteurs moléculaires de la famille de Grb7

Carré, Nadège; Goenaga, Diana; Burnol, Anne-Françoise

doi:10.1007/s11690-011-0280-y

Cited by 2 publications

(1 citation statement)

References 56 publications

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“…44,45 Moreover, the members of the Grb7 family of adapters (Grb10 and Grb14) function as negative modulators of insulin signaling by binding with activated IR. [46][47][48] Overexpression of Grb10 or Grb14 in cultured cell line inhibited phosphorylation of IRS1, 49,50 whereas the knockout of Grb14 improves insulin signaling in the liver and skeletal muscle with no significant changes in cardiac function, 51 supporting Grb14 inhibition as an effective therapeutic target. Various Grb2 inhibitors have been proven effective in treating human cancer by targeting Grb2 signaling either through blocking its connection with cell surface kinases or compromising its interlink to downstream pathways.…”

Section: Discussionmentioning

confidence: 99%

Sustained Stimulation of β2AR Inhibits Insulin Signaling in H9C2 Cardiomyoblast Cells Through the PKA-Dependent Signaling Pathway

Pei¹,

Xiao²,

Guo³

et al. 2020

DMSO

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Introduction: This study aimed to investigate the role of β 2 adrenergic receptor (β 2 AR) in insulin signaling transduction in H9C2 cardiomyoblast cells to understand the formation of the β 2 AR-insulin receptor (IR) protein complex and its role in insulin-induced Glut4 expression. Methods: H9C2 cells were treated with various protein inhibitors (CGP, β 1 AR inhibitor CGP20712; ICI, β 2 AR inhibitor ICI 118,551; PKI, PKA inhibitor myristoylated PKI; PD 0325901, MEK inhibitor; SP600125, JNK inhibitor) with or without insulin or isoproterenol (ISO) before RNA-sequencing (RNA-Seq) and quantitative-PCR (Q-PCR). Yeast twohybrid, co-immunoprecipitation and His-tag pull-down assay were carried out to investigate the formation of the β 2 AR-IR protein complex. The intracellular concentrations of cAMP in H9C2 cells were tested by high performance liquid chromatography (HPLC) and the phosphorylation of JNK was tested by Western blot. Results: Gene Ontology (GO) analysis revealed that the most significantly enriched processes in the domain of molecular function (MF) were catalytic activity and binding, whereas in the domain of biological processes (BP) were metabolic process and cellular process. Furthermore, the enriched processes in the domain of cellular components (CC) were cell and cell parts. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the most significant pathways that have been altered included the PI3K-Akt and MAPK signaling pathways. Q-PCR, which was performed to verify the gene expression levels exhibited consistent results. In evaluating the signaling pathways, the sustained stimulation of β 2 AR by ISO inhibited insulin signalling, and the effect was primarily through the cAMP-PKA-JNK pathway and MEK/JNK signaling pathway. Yeast two-hybrid, coimmunoprecipitation and His-tag pull-down assay revealed that β 2 AR, IR, insulin receptor substrate 1 (IRS1), Grb2-associated binding protein 1 (GAB1) and Grb2 existed in the same protein complex. Conclusion: The sustained stimulation of β 2 AR might inhibit insulin signaling transduction through the cAMP-PKA-JNK and MEK/JNK pathways in H9C2 cells.

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Section: Discussionmentioning

confidence: 99%

Sustained Stimulation of β2AR Inhibits Insulin Signaling in H9C2 Cardiomyoblast Cells Through the PKA-Dependent Signaling Pathway

Pei¹,

Xiao²,

Guo³

et al. 2020

DMSO

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Current Studies on Molecular Mechanisms of Insulin Resistance

Pei

Wang

2022

Journal of Diabetes Research

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Diabetes is a metabolic disease that raises the risk of microvascular and neurological disorders. Insensitivity to insulin is a characteristic of type II diabetes, which accounts for 85-90 percent of all diabetic patients. The fundamental molecular factor of insulin resistance may be impaired cell signal transduction mediated by the insulin receptor (IR). Several cell-signaling proteins, including IR, insulin receptor substrate (IRS), and phosphatidylinositol 3-kinase (PI3K), have been recognized as being important in the impaired insulin signaling pathway since they are associated with a large number of proteins that are strictly regulated and interact with other signaling pathways. Many studies have found a correlation between IR alternative splicing, IRS gene polymorphism, the complicated regulatory function of IRS serine/threonine phosphorylation, and the negative regulatory role of p85 in insulin resistance and diabetes mellitus. This review brings up-to-date knowledge of the roles of signaling proteins in insulin resistance in order to aid in the discovery of prospective targets for insulin resistance treatment.

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Modulation de la sensibilité à l’insuline par les adapteurs moléculaires de la famille de Grb7

Cited by 2 publications

References 56 publications

<p>Sustained Stimulation of β<sub>2</sub>AR Inhibits Insulin Signaling in H9C2 Cardiomyoblast Cells Through the PKA-Dependent Signaling Pathway</p>

<p>Sustained Stimulation of β<sub>2</sub>AR Inhibits Insulin Signaling in H9C2 Cardiomyoblast Cells Through the PKA-Dependent Signaling Pathway</p>

Current Studies on Molecular Mechanisms of Insulin Resistance

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