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Igf1 receptor

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https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#1
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28532828/expression-of-apelin-and-apelin-receptor-apj-in-porcine-ovarian-follicles-and-in%C3%A2-vitro-effect-of-apelin-on-steroidogenesis-and-proliferation-through-apj-activation-and-different-signaling-pathways
#2
A Rak, E Drwal, Ch Rame, K Knapczyk-Stwora, M Słomczyńska, J Dupont, E L Gregoraszczuk
Apelin was thought to be an adipocyte-specific hormone, but recent studies indicate a link between apelin and female reproductive function. Using real-time PCR, immunoblotting, immunohistochemistry and ELISA, we demonstrated expression of apelin and its receptor (APJ) in ovarian follicles of different sizes from mature pigs. Apelin concentration in the follicular fluid, and expression of both apelin and APJ, increased with follicular growth; greatest values were found in large follicles. Immunohistochemistry revealed the positive staining for apelin and APJ in membranes of granulosa, than theca cells...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28500773/the-energy-sensing-lkb1-ampk%C3%AE-1-pathway-regulates-igf1-secretion-and-consequent-activation-of-the-igf1r-pkb-pathway-in-primary-hepatocytes
#3
Liang Chen, Qiaoli Chen, Ping Rong, Hong Yu Wang, Shuai Chen
The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular mechanisms regulating of its secretion is not fully understood. The AMP-activated protein kinase (AMPK) is a key energy sensor, and accumulative evidence shows that AMPK is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse primary hepatocytes...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28474384/exploring-genetic-susceptibility-to-obesity-through-genome-functional-pathway-analysis
#4
Alexander P Gabrielli, Ann M Manzardo, Merlin G Butler
OBJECTIVE: Obesity has been reaching epidemic levels in recent decades, with a growing body of research identifying predisposing genetic components. To explore the relationship of genetic factors contributing to obesity, an analytical computer-based gene-profiling approach utilizing an updated list of clinically relevant and known obesity-related genes was undertaken. METHODS: An updated list of 494 genes reportedly associated with obesity was compiled, and the GeneAnalytics profiling software was utilized to interrogate genomic databases from GeneCards® to cross-reference obesity gene sets against tissues and cells, diseases, genetic pathways, gene ontology (GO)-biological processes and GO-molecular functions, phenotypes, and compounds...
May 5, 2017: Obesity
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#5
Maria Schindler, Mareike Pendzialek, Katarzyna Joanna Grybel, Tom Seeling, Jacqueline Gürke, Bernd Fischer, Anne Navarrete Santos
STUDY QUESTION: How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts? SUMMARY ANSWER: In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover. WHAT IS KNOWN ALREADY: Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available...
May 4, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28462703/divergent-roles-of-irs-insulin-receptor-substrate-1-and-2-in-liver-and-skeletal-muscle
#6
Sabine Eckstein, Cora Weigert, Rainer Lehmann
IRS1 and IRS2 are the most important representatives of the IRS protein family and critical nodes in insulin/IGF1-signalling. Although they are quite similar in their structural and functional features they show tissue-specific differences. In this review we outline the functions of IRS1 and IRS2 in skeletal muscle and liver with regard to their importance for metabolism, growth and differentiation. Mechanisms contributing to IRS1 and IRS2 dysregulation in disease states as well as consequences thereof are discussed...
April 26, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#7
Nathan C Law, Elyse M Donaubauer, Anthony J Zeleznik, Mary Hunzicker-Dunn
Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation...
April 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28456720/regulation-of-tight-junction-integrity-by-insulin-in-an-in-vitro-model-of-human-blood-brain-barrier
#8
Shingo Ito, Mari Yanai, Shunsuke Yamaguchi, Pierre-Olivier Couraud, Sumio Ohtsuki
Although insulin receptor is expressed at the human blood-brain barrier (BBB), the physiological and pathological roles of insulin signaling in biological responses at the BBB remain unclear. Here, we investigate insulin signaling at the human BBB using human cerebral microvascular endothelial cell line hCMEC/D3 as a well-established in vitro model. Western blot analysis showed that insulin induced phosphorylation of ERK1/2 and IRS-1 in hCMEC/D3 cells. Short-term insulin stimulation increased cell proliferation via the canonical PI-3K/AKT and MAPK signaling pathways, suggesting that insulin signaling is involved in the regulation of biological responses in the human BBB...
April 26, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28454409/expression-of-imp3-as-a-marker-for-predicting-poor-outcome-in-gastroenteropancreatic-neuroendocrine-neoplasms
#9
Li-Mian Er, Yong Li, Ming-Li Wu, Qun Zhao, Bi-Bo Tan, Xiao-Ling Wang, Shi-Jie Wang
The aim of the present study was to investigate the expression and clinical significance of oncofetal protein insulin-like growth factor (IGF) II mRNA-binding protein 3 (IMP3) in the differentiation of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). A total of 162 patients who were diagnosed with GEP-NEN, and who underwent surgical or endoscopic resection from January 2006 to March 2013, were enrolled in the study, including 85 cases of grade (G)1 neuroendocrine tumors, 40 cases of G2 neuroendocrine tumors, 28 cases of G3 neuroendocrine carcinomas and 9 cases of mixed stage adenoneuroendocrine carcinomas...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28444169/androgen-receptor-regulation-of-local-growth-hormone-in-prostate-cancer-cells
#10
M V Recouvreux, B Wu, A C Gao, S Zonis, V Chesnokova, N Bhowmick, L W Chung, S Melmed
Prostate cancer (PCa) growth is mainly driven by androgen receptor (AR), and tumors that initially respond to androgen deprivation therapy (ADT) or AR inhibition usually relapse into a more aggressive, castration resistant stage (CRPC). Circulating growth hormone (GH) has a permissive role in PCa development in animal models and in human PCa xenograft growth. As GH and GH receptor (GHR) are both expressed in PCa cells, we assessed whether prostatic GH production is linked to AR activity and whether GH contributes to the castration resistant phenotype...
April 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28439815/the-effects-of-voluntary-physical-exercise-activated-neurotrophic-signaling-in-rat-hippocampus-on-mrna-levels-of-downstream-signaling-molecules
#11
Christina A E Solvsten, Tina F Daugaard, Yonglun Luo, Frank de Paoli, Jane H Christensen, Anders L Nielsen
Physical exercise results in the increased expression of neurotrophic factors and the subsequent induction of signal transduction cascades with a positive impact on neuronal functions. In this study, we used a voluntary physical exercise rat model to determine correlations in hippocampus mRNA expression of the neurotropic factors Bdnf, VegfA, and Igf1; their receptors TrkB, Igf1R, VegfR1, and VegfrR2; and downstream signal transducers Creb, Syn1, and Vgf. In hippocampi of physically exercised rats, the mRNA expression levels of Bdnf transcript 4 (Bdnf-t4), VegfA, and Igf1, as well as VegfR1, TrkB, Creb, Vgf, and Syn1, were increased...
April 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28439104/a-novel-5ht3-receptor-igf1-mechanism-distinct-from-ssri-induced-antidepressant-effects
#12
M Kondo, Y Koyama, Y Nakamura, S Shimada
Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28431247/the-ubiquitin-ligase-chip-integrates-proteostasis-and-aging-by-regulation-of-insulin-receptor-turnover
#13
Riga Tawo, Wojciech Pokrzywa, Éva Kevei, Melek E Akyuz, Vishnu Balaji, Svenja Adrian, Jörg Höhfeld, Thorsten Hoppe
Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28416760/the-histone-demethylase-kdm3a-regulates-the-transcriptional-program-of-the-androgen-receptor-in-prostate-cancer-cells
#14
Stephen Wilson, Lingling Fan, Natasha Sahgal, Jianfei Qi, Fabian V Filipp
The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410230/insulin-growth-factor-binding-protein-2-mediates-the-progression-of-lymphangioleiomyomatosis
#15
Xiangke Li, Xiaolei Liu, Linda Zhang, Chenggang Li, Erik Zhang, Wang Ma, Qingxia Fan, Jane J Yu
Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease that almost exclusively affects women. LAM cells migrate to the lungs, where they cause cystic destruction of lung parenchyma. Mutations in TSC1 or TSC2 lead to the activation of the mammalian target of rapamycin complex-1, a kinase that regulates growth factor-dependent protein translation, cell growth, and metabolism. Insulin-like growth factor binding protein 2 (IGFBP2) binds insulin, IGF1 and IGF2 in circulation, thereby modulating cell survival, migration, and invasion in neoplasms...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406532/endometrial-gene-expression-in-primiparous-dairy-cows-at-the-end-of-the-voluntary-waiting-period-is-affected-by-nutrition-total-mixed-ration-vs-increasing-levels-of-herbage-allowance
#16
A L Astessiano, M Carriquiry, D A Mattiauda, M L Adrien, P Chilibroste, A Meikle
The study postulated that differential nutritional management during the early lactation period would be reflected in endometrial expression of genes related to embryo growth at the end of the voluntary waiting period. Thus, the effect of the combined use of total mixed ration (TMR) and grazing under different herbage allowances during the first 75 days post-partum (DPP) on endometrial gene expression was evaluated in primiparous dairy cows. Cows were blocked by body weight, age and body condition score and randomly assigned to three grazing treatments: high (HA, 30 kg DM per cow per day), medium (MA, 15 kg DM per cow per day) and low (LA, 7...
April 12, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28402847/igf1-shapes-macrophage-activation-in-response-to-immunometabolic-challenge
#17
Olga Spadaro, Christina D Camell, Lidia Bosurgi, Kim Y Nguyen, Yun-Hee Youm, Carla V Rothlin, Vishwa Deep Dixit
In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptors from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure, and led to insulin resistance in mice fed a high-fat diet...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28394183/assessing-the-impact-of-insulin-glargine-and-detemir-treatment-to-serum-total-igf1-levels-in-the-insulin-naive-type-2-diabetic-patients
#18
Soner Cander, Ozen Oz Gul, Oguzhan Sitki Dizdar, Nizameddin Koca, Taner Aydın, Emre Sarandol, Canan Ersoy
AIM: The mitogenic potential of analog insulins due to their different insulin-like growth factor-1 (IGF1) receptor affinity is a situation that causes concern related to cancer risk. We aimed to examine the changes in the serum IGF1 levels formed by insulin glargine and detemir in the insulin-naive type 2 diabetic patients. METHODS: The serum total IGF1 levels of the 62 insulin-naive type 2 diabetic patients were studied before and after 12 weeks of the started treatment with basal insulin analogs...
June 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28389567/large-scale-analysis-of-variation-in-the-insulin-like-growth-factor-family-in-humans-reveals-rare-disease-links-and-common-polymorphisms
#19
Peter Rotwein
The insulin-like growth factors IGF1 and IGF2 are closely related proteins that are essential for normal growth and development in humans and other species and play critical roles in many physiological and patho-physiological processes. IGF actions are mediated by trans-membrane receptors and modulated by IGF binding proteins. The importance of IGF actions in human physiology is strengthened by the rarity of inactivating mutations in their genes, and by the devastating impact caused by such mutations on normal development and somatic growth...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28373074/netrin-1-mediates-protective-effects-exerted-by-insulin-like-growth-factor-1-on-cochlear-hair-cells
#20
Kohei Yamahara, Takayuki Nakagawa, Juichi Ito, Kazuo Kinoshita, Koichi Omori, Norio Yamamoto
Sensorineural hearing loss (SNHL) is mainly caused by the damage of cochlear hair cells (HCs). As HCs and supporting cells (SCs) do not proliferate in postnatal mammals, the loss of HCs and SCs is irreversible, emphasizing the importance of preserving their numbers to prevent SNHL. It is known that insulin-like growth factor 1 (IGF1) is instrumental in the treatment of SNHL. Our previous study indicates that IGF1 protects HCs against aminoglycoside by activating IGF1 receptor and its two major downstream pathways, PI3K/AKT and MEK/ERK, in SCs, which results in the upregulation of the expression of the Netrin1-encoding gene (Ntn1)...
April 1, 2017: Neuropharmacology
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