• mTORC1 contributes to insulin resistance by causing proteasomal degradation of insulin receptor substrate (IRS) proteins, such as IRS1, which are necessary for the recruitment of PI3K to growth factor receptors. (sciety.org)
  • Metabolic syndrome (syndrome X, insulin resistance) is a multifactorial disease with multiple risk factors that arises from insulin resistance accompanying abnormal adipose deposition and function. (medscape.com)
  • Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes. (jci.org)
  • In this review, we discuss potential mechanisms by which brief nutrient excess and obesity lead to insulin resistance and propose that these mechanisms of action are different but interrelated. (jci.org)
  • We then discuss how obesity leads to insulin resistance via a complex interplay among systemic fatty acid excess, microhypoxia in adipose tissue, ER stress, and inflammation. (jci.org)
  • In particular, we focus on the hypothesis that the macrophage is an important cell type in the propagation of inflammation and induction of insulin resistance in obesity. (jci.org)
  • Insulin resistance is defined as an inadequate response by insulin target tissues, such as skeletal muscle, liver, and adipose tissue, to the physiologic effects of circulating insulin. (jci.org)
  • The causes of insulin resistance can be genetic and/or acquired. (jci.org)
  • Nonetheless, it is likely that any genetic component must interact with environmental factors in order for insulin resistance to develop into a pathophysiologically meaningful abnormality. (jci.org)
  • In the presence of a robust compensatory insulin secretory response to insulin resistance, glucose levels can remain relatively normal. (jci.org)
  • Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. (who.int)
  • This study confirms that insulin resistance affects treatment outcome, and thus HOMA-IR testing before initiation of therapy may be a cost-effective tool. (who.int)
  • 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. (who.int)
  • conditions such as insulin resistance in the most prevalent genotype in Egypt patients with HCV infection. (who.int)
  • Adding to this grow- genotype 4, to assess factors associated proportion of Egyptians estimated to be ing body of evidence, it is now suggested with insulin resistance in those patients chronically infected was 9.8% ( 1 ). (who.int)
  • Depending upon the receptor, IRS2 undergoes phosphorylation, either via Tyk2 following type I IFN binding, or via JAK1 and 3 following IL-4, -7 and -15 binding. (rndsystems.com)
  • This was associated with DIM‐enhanced phosphorylation of the signaling intermediates Akt, insulin receptor substrate‐1, and insulin receptor early in differentiation. (researchgate.net)
  • It is worth noting that we have found the key upstream target of DOX-induced HF, PTP1B, which inhibits the expression of HIF-1α by inhibiting the phosphorylation of IRS, leading to disorders of fatty acid metabolism and glycolysis, which together with the decrease of Nrf2, SOD, Cytc, and AK4 proteins lead to oxidative stress. (frontiersin.org)
  • Akt activation leads to the phosphorylation and inactivation of various downstream targets, including glycogen synthase kinase 3 (GSK3), which regulates glycogen synthesis, and the mammalian target of rapamycin (mTOR), which controls protein synthesis and cell growth. (ebiwinner.com)
  • IRS2 (insulin receptor substrate 2) is a 180-190 kDa substrate intermediate that lies between various cytokine receptors and downstream signaling molecules. (rndsystems.com)
  • The Igf 1 receptor signaling pathway regulates cell growth and survival by activating downstream signaling molecules that promote cell proliferation, inhibit apoptosis, and stimulate protein synthesis. (ebiwinner.com)
  • Potential therapeutic targets in the Igf 1 receptor signaling pathway include the IGF-1 receptor itself, as well as downstream signaling molecules such as PI3K, AKT, and mTOR. (ebiwinner.com)
  • Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. (researchgate.net)
  • Conclusions Our findings suggest that DIM may improve insulin sensitivity through the activation of the insulin signaling pathway, leading to enhanced glucose uptake. (researchgate.net)
  • DIM, a major metabolite of indole-3-carbinol, which is naturally produced in broccoli and cabbage, enhances glucose uptake through the improvement of insulin sensitivity in 3T3-L1 cells [13] . (researchgate.net)
  • Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity. (jci.org)
  • The hallmarks of impaired insulin sensitivity in these three tissues are decreased insulin-stimulated glucose uptake into skeletal muscle, impaired insulin-mediated inhibition of hepatic glucose production in liver, and a reduced ability of insulin to inhibit lipolysis in adipose tissue. (jci.org)
  • These proteins are novel isoforms of the actin-bundling protein espin that arise through the use of a unique site for transcriptional initiation and differential splicing. (northwestern.edu)
  • This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN , which encodes a calcium-insensitive actin-bundling protein called espin. (bmj.com)
  • Previous studies have found that DIM can improve type 2 diabetes by enhancing glucose uptake through the activation of insulin signaling in 3T3-L1 cells, and by lowering the plasma glucose levels in high-fat-diet-fed obese mice [13, 14]. (researchgate.net)
  • Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (embl.de)
  • Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (embl.de)
  • The phosphoinositide 3-kinase (PI3K)/AKT pathway plays crucial roles in cell viability and protein synthesis and is frequently co-opted by viruses to support their replication. (sciety.org)
  • They act as mediators between multiple growth factor receptors that possess tyrosine kinase activity, such as the insulin and insulin growth factor receptors, and a complex network of intracellular signalling molecules, resulting in activation of, for example, the PI3K and RAS/ERK pathways and subsequent transcription of target genes. (atlasgeneticsoncology.org)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • The key components of the Igf 1 receptor signaling pathway include the IGF-1 receptor, insulin receptor substrate proteins (IRS), phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). (ebiwinner.com)
  • One key insight into the Igf 1 receptor signaling pathway is the involvement of phosphoinositide 3-kinase (PI3K) and Akt. (ebiwinner.com)
  • Upon activation of the receptor, PI3K is recruited to the receptor complex and phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). (ebiwinner.com)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • The insulin receptor substrate p53 (IRSp53), an Src homology 3 (SH3) adapter protein and regulator of the actin cytoskeleton, was identified as an espin-binding protein in yeast two-hybrid screens. (northwestern.edu)
  • Insulin-like growth factor-1 (IGF-1), a member of a family of growth factors that are structurally closely related to pro-insulin, has shown profound effects on chondrocyte biological behavior and fundamentally regulates cartilage matrix metabolism during cartilage repair. (biomedcentral.com)
  • In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. (researchgate.net)
  • Dysregulation of the Igf 1 receptor signaling pathway has been implicated in various diseases, including cancer, diabetes, and neurodegenerative disorders. (ebiwinner.com)
  • In a cross-sectional study of 48 AD patients without diabetes, 20 cognitively normal diabetic patients, 16 patients with frontotemporal dementia, and 84 cognitively normal controls, researchers found that dysfunctionally phosphorylated insulin receptor substrate-1 (IRS-1), a neuronal protein, is detectable in blood using exosome-based technology and may be able to predict AD up to 10 years before the appearance of symptoms. (medscape.com)
  • The IGF-1 receptor signaling pathway plays a crucial role in cell growth, proliferation, and survival. (ebiwinner.com)
  • The Igf 1 receptor signaling pathway is regulated by various mechanisms, including ligand availability, receptor expression and activation, as well as negative feedback loops and cross-talk with other signaling pathways. (ebiwinner.com)
  • Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. (who.int)
  • Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
  • The physiological functions of the Igf 1 receptor signaling pathway include regulation of growth and development, metabolism, tissue repair, and immune function. (ebiwinner.com)
  • The Igf 1 receptor signaling pathway is a cellular signaling pathway that is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor on the cell surface. (ebiwinner.com)
  • How does the Igf 1 receptor signaling pathway regulate cell growth and survival? (ebiwinner.com)
  • This pathway is activated by the binding of insulin-like growth factor 1 (IGF-1) to its receptor, leading to the activation of downstream signaling cascades. (ebiwinner.com)
  • The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. (biomedcentral.com)
  • IGF-1 is a member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. (biomedcentral.com)
  • Current research efforts in the field of Igf 1 receptor signaling pathway are focused on understanding the molecular mechanisms underlying its regulation, identifying novel therapeutic targets, and developing strategies to modulate its activity for the treatment of various diseases. (ebiwinner.com)
  • Our results establish espin as an essential protein for hearing and vestibular function in humans. (bmj.com)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
  • In conclusion, the Igf 1 receptor signaling pathway is a complex and highly regulated pathway that plays a critical role in various biological processes. (ebiwinner.com)
  • Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (embl.de)
  • However, gut senescence does not appear to be the direct cause for longevity regulation, as knockdown of both hormone receptors did not affect adult lifespan. (bioone.org)
  • Thus, the PC espins exhibit the properties of modular actin-bundling proteins with the potential to influence the organization and dynamics of the actin cytoskeleton in PC dendritic spines and to participate in multiprotein complexes involving SH3 domain-containing proteins, such as IRSp53. (northwestern.edu)
  • The results showed that a total of 278 proteins with significant changes were identified by quantitative proteomic analysis, of which 118 proteins were significantly upregulated and 160 proteins were significantly downregulated in myocardial tissue. (frontiersin.org)
  • These results indicate that the two intestinal secretory peptides antagonistically regulate adult lifespan and intestinal senescence through multiple pathways, irrespective of insulin, which implicates a complementary gradient distribution of each of the hormone-producing EEs, consistent with local requirements for cell activity along the posterior midgut. (bioone.org)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor beta locus. (atlasgeneticsoncology.org)
  • This effect on longevity is apparently correlated with the midgut senescence phenotypes as a result of direct hormone action through both hormone receptors expressed in the enteroblasts or other midgut cell types. (bioone.org)
  • It is the primary IRS protein found in hematopoietic cells. (rndsystems.com)
  • We identified a group of actin-binding-bundling proteins that are expressed in cerebellar Purkinje cells (PCs) but are not detected in other neurons of the CNS. (northwestern.edu)
  • Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
  • We discuss how pathways that "sense" nutrients within skeletal muscle are readily able to regulate insulin action. (jci.org)
  • HCV is currently the most sig- insulin levels fail to achieve normal glu- tion therapy are a feasible approach for nificant health problem in Egypt. (who.int)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class. (embl.de)
  • Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)