China
Africa
Explore chapters and articles related to this topic
Neuroendocrine Interactions in the Control of Glucose- and Energy Homeostasis
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Upon binding of the extracellular α-subunits of its receptor, insulin induces the dimerization and autophosphorylation of the intracellular β-subunits, followed by tyrosine phosphorylation of insulin receptor substrate proteins, phosphoinositide 3-kinase (PI3K) activation and AKT phosphorylation. All of the major components of insulin signalling found in the periphery are also present in the brain. One signalling node that may be of particular interest for the central regulation of whole-body energy and glucose homeostasis is the enzyme glycogen synthase kinase-3β (GSK-3β). In the periphery, GSK3β is a crucial enzyme in glycogen synthesis and it is activated by glucose 6 phosphate (16). Stimulation of insulin signalling results in inhibition of GSK-3β (17–19). Pharmacological inhibition of GSK-3β in the brain has been demonstrated to rescue PI3K-AKT signalling and improve glucose homeostasis in obese and glucose-intolerant rodent models, while adeno-associated virus-mediated overexpression in the hypothalamus impaired glucose tolerance (20, 21). These findings suggest that central GSK-3β is a potent modulator of insulin sensitivity.
ras-p21 Proteins: Switch Devices for Signal Transduction
Published in Juan Carlos Lacal, Frank McCormick, The ras Superfamily of GTPases, 2017
Antonio Cuadrado, Amancio Carnero, Juan Carlos Lacal
Tyrosine phosphorylation is an important event associated to cell differentiation and development in a variety of cell systems. Also shown to be important for some of these events are ras proteins. For instance, when ras oncogenes were introduced into the rat pheochromocytoma cell line PC12, these cells produced neurite outgrowth and differentiation to sympathetic neurons in a way similar to NGF.113-115 These ras proteins have been also implicated in the differentiation program of other cell systems, such as lymphoid, endocrine, adi-pocite, and muscle cells.116-119
Protein Phosphorylation
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
A subfamily of SH2 domains is found specifically in protein-tyrosine phosphatases.468 Activation of these enzymes depends on tyrosine phosphorylation,469 and tyrosine phosphatases containing SH2 domains may be a target of tyrosine kinases. One of these enzymes, Syp, contains two SH2 domains and is rapidly phosphorylated on tyrosine in EGF- and PDGF-stimulated cells.470 Syp exhibits homology to the product of the corkscrew (csw) gene of Drosophila, which is required for signal transduction downstream of the Torso receptor tyrosine kinase of the insect.471 The Syp gene is widely expressed throughout mouse embryonic development as well as in adult mouse tissues. The activity of some tyrosine phosphatases may link growth factor receptors and other signaling cellular proteins with tyrosine kinase activity for the regulation of signal transduction and other related functions through phosphorylation/dephosphorylation of tyrosine.
An evaluation of ponatinib as a therapy in adult patients with resistant/intolerant chronic-phase chronic myeloid leukemia
Published in Expert Review of Hematology, 2022
Jay Yang, Malini Surapaneni, Charles A. Schiffer
Receptor tyrosine kinases (RTKs) are polypeptide proteins with the ability to dimerize and transfer phosphate groups from ATP to tyrosine residues upon activation by a stimulating growth factor. Once tyrosine phosphorylation occurs, it results in recognition by cytoplasmic SH2 domains which causes intracellular signal transduction, generally utilizing STAT, RAS, or PI3K pathways ultimately leading to cell proliferation and survival [38]. In CML, the t(9;22)(q34;q11) causes the ABL1 proto-oncogene to be placed in proximity with BCR resulting in a constitutively activated RTK. TKIs target the ATP binding site on the BCR-ABL1 RTK as competitors and arrest phosphorylation [39]. However, mutations in the ABL1 kinase domain can result in resistance to imatinib and second-generation TKIs [26].
The impact of the gut microbiota on the reproductive and metabolic endocrine system
Published in Gut Microbes, 2021
Xinyu Qi, Chuyu Yun, Yanli Pang, Jie Qiao
Insulin is an important hormone that increases membrane permeability to glucose and lowers the level of glucose by activating the insulin receptor. The binding of insulin to insulin receptors causes the activation of insulin receptor tyrosine kinase and the tyrosine phosphorylation of insulin receptor and insulin receptor substrate (IRS) proteins.80,81 Phosphorylation of IRS stimulates the binding of the lipid kinase phosphatidylinositol-3-kinase (PI3-K) at the plasma membrane, which phosphorylates the Thr308 residue of AKT by synthesizing Ptdlns(3,4,5)P3 (PIP3).82 AKT activation leads to glucose production, utilization and uptake, as well as the synthesis of glycogen, lipids, and proteins.82 Interestingly, mounting evidence suggests that the gut microbiome, as well as the metabolites of bacteria, are involved in the progression of insulin resistance.57,83,84
High-fat diet effects on the prostatic adenocarcinoma model and jaboticaba peel extract intake: protective response in metabolic disorders and liver histopathology
Published in Nutrition and Cancer, 2020
Ellen Nogueira-Lima, Celina de Almeida Lamas, Andressa Mara Baseggio, Jéssica Stephany Fernandes do Vale, Mário Roberto Maróstica Junior, Valéria Helena Alves Cagnon
The insulin receptor 1 (IRS-1) plays a critical role in the activation of liver insulin signaling together with insulin receptor 2 (IRS-2) (53). IRS tyrosine-phosphorylation is necessary for insulin signaling propagation in the cell and its decrease is correlated with IR. Recently, the literature demonstrated that polyphenols could increase the pIRS-1 protein levels in the liver in high-fat-fed mice (54). However, Honma and collaborators studied the IRS-1 and IRS-2 expression in the liver of patients with NAFLD and steatosis (55) and demonstrated that there were no changes in IRS-1 mRNA, in contrast to IRS-2, which demonstrated a significant decrease (55). In addition, the literature showed that IRS1 and IRS2 roles in insulin signaling could be tissue specific (53). According to these authors, mice with IRS1 mutation presented a systemic IR, interfering in the insulin signaling in the liver, skeletal muscle and adipose tissue (53). However, in the IRS2 mutation mice, IR occurred primarily in the liver through IRS2 signaling, which demonstrated its importance in this pathway (56). Thus, taking into consideration the results above-mentioned, we suggest that systemic IR improvement after PJE treatment could not be linked just to pIRS1 liver levels and lipid accumulation decreased which were observed in this study, but could be linked to other insulin receptors. However, more studies are required regarding IR signaling in the liver, particularly in mice, which have PCa.