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https://www.readbyqxmd.com/read/28432521/intermittent-food-restriction-initiated-late-in-life-prolongs-lifespan-and-retards-the-onset-of-age-related-markers-in-the-annual-fish-nothobranchius-guentheri
#1
Xia Wang, Xiaoyuan Du, Yang Zhou, Su Wang, Feng Su, Shicui Zhang
Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3...
April 21, 2017: Biogerontology
https://www.readbyqxmd.com/read/28427228/mir-29a-regulated-er-positive-breast-cancer-cell-growth-and-invasion-and-is-involved-in-the-insulin-signaling-pathway
#2
Zhi-Hua Li, Qiu-Yun Xiong, Liang Xu, Peng Duan, Qianwen Ou Yang, Ping Zhou, Jian-Hong Tu
Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427155/update-of-igf-1-receptor-inhibitor-ganitumab-dalotuzumab-cixutumumab-teprotumumab-and-figitumumab-effects-on-cancer-therapy
#3
REVIEW
Xiao Qu, Zhinan Wu, Wei Dong, Tiehong Zhang, Liguang Wang, Zhaofei Pang, Wei Ma, Jiajun Du
BACKGROUND: Prognostic studies of insulin-like growth factor-1 receptor(IGF-1R) inhibitors in cancer therapy had promising results in infratests, which exhibited that IGF-1R signalling was crucial in cancer cells growth. However, the conclusion of later clinical trials revealed a dim future for IGF-1R inhibitors to treat cancer. We conducted this analysis to figure out how IGF-1R inhibitors acted in clinical cancer therapy. MATERIAL AND METHODS: We searched up-to-date studies about the single agent of IGF-1R inhibitors or combination with other therapies in solid tumor...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424159/prolonged-elimination-of-negative-feedback-control-mechanisms-along-the-insulin-signalling-pathway-impairs-%C3%AE-cell-function-in-vivo
#4
Roi Isaac, Yaron Vinik, Sigalit Boura-Halfon, Lydia Farack, Sarina Streim, Eytan Elhanany, Zvi Kam, Yehiel Zick
Cellular stress and pro-inflammatory cytokines induce phosphorylation of insulin receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-1 signalling. We therefore examined the effects of mutation of five 'inhibitory' Ser phosphorylation sites on IRS2 function in transgenic mice that overexpress, selectively in pancreatic β cells, either wild-type (WT) or a mutated IRS2 protein (IRS2(5A)). Islets size, number, and mRNA levels of catalase and superoxide dismutase, were increased, while those of nitric oxide synthase were decreased in 7-10 weeks old IRS2(5A)-β mice compared to IRS2(WT)-β mice...
April 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28421341/insufficient-activation-of-akt-upon-reperfusion-because-of-its-novel-modification-by-reduced-pp2a-b55%C3%AE-contributes-to-enlargement-of-infarct-size-by-chronic-kidney-disease
#5
Toshiyuki Tobisawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Yukishige Kimura, Satoko Ishikawa, Hidemichi Kouzu, Keitaro Nishizawa, Hideaki Yoshida, Tetsuji Miura
Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28420927/in-silico-analysis-of-fragile-histidine-triad-involved-in-regression-of-carcinoma
#6
Muhammad Asif Rasheed, Fatima Tariq, Sara Afzal, Shazia Mannanv
Hepatocellular carcinoma (HCCa) is a primary malignancy of the liver. Many different proteins are involved in HCCa including insulin growth factor (IGF) II , signal transducers and activators of transcription (STAT) 3, STAT4, mothers against decapentaplegic homolog 4 (SMAD 4), fragile histidine triad (FHIT) and selective internal radiation therapy (SIRT) etc. The present study is based on the bioinformatics analysis of FHIT protein in order to understand the proteomics aspect and improvement of the diagnosis of the disease based on the protein...
April 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28420864/insulin-growth-factor-1-protects-neural-stem-cells-against-apoptosis-induced-by-hypoxia-through-akt-mitogen-activated-protein-kinase-extracellular-signal-regulated-kinase-akt-mapk-erk-pathway-in-hypoxia-ishchemic-encephalopathy
#7
Bing Zhao, Zebao Zheng
BACKGROUND Insulin growth factor 1 (IGF-1) is reported to modulate cell growth and acts as potential therapy for traumatic brain injury. This study was designed to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem cells (NSCs). MATERIAL AND METHODS A hypoxia model was constructed using NSCs separated from the hippocampus of rat. NSCs were divided into four groups: cells under normoxic conditions that acted as controls (C group), cells under hypoxia (H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the IGF-1 receptor (HIP group)...
April 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28419894/muscle-cell-communication-in-development-and-repair
#8
REVIEW
Alexis R Demonbreun, Elizabeth M McNally
Under basal conditions, postnatal skeletal muscle displays little cell turnover. With injury, muscle initiates a rapid repair response to reseal damaged membrane, reactivating many developmental pathways to facilitate muscle regeneration and prevent tissue loss. Muscle precursor cells become activated accompanied by differentiation and fusion during both muscle growth and regeneration; inter-cellular communication is required for successful completion of these processes. Cellular communication is mediated by lipids, fusogenic membrane proteins, and exosomes...
April 15, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28414818/tgf%C3%AE-smad3-regulates-proliferation-and-apoptosis-through-irs-1-inhibition-in-colon-cancer-cells
#9
Katie L Bailey, Ekta Agarwal, Sanjib Chowdhury, Jiangtao Luo, Michael G Brattain, Jennifer D Black, Jing Wang
In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation of TGFβ activation leads to elevated expression and phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell proliferation, decreased apoptosis and increased tumor growth in vitro and in vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated oncogenic phenotypes, indicating that TGFβ/Smad3 signaling inhibits cell proliferation and increases apoptosis at least partially through the inhibition of IRS-1 expression and activation...
2017: PloS One
https://www.readbyqxmd.com/read/28410970/insulin-and-insulin-like-growth-factor-1-modulate-the-lipolytic-action-of-growth-hormone-by-altering-signal-pathway-linkages
#10
Heather E Bergan-Roller, Alicia T Ickstadt, Jeffrey D Kittilson, Mark A Sheridan
Growth hormone (GH) has many actions in vertebrates, including the regulation of two disparate metabolic processes: growth promotion (anabolic) and th e mobilization of stored lipids (catabolic). Our previous studies showed that GH stimulated IGF-1 production in hepatocytes from fed rainbow trout, but in cells from fasted fish GH stimulated lipolysis. In this study, we used rainbow trout (Oncorhynchus mykiss) to elucidate regulation of the mechanisms that enable cells to alter their lipolytic responsiveness to GH...
April 11, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28410423/daf-18-pten-signals-through-aak-1-ampk-to-inhibit-mpk-1-mapk-in-feedback-control-of-germline-stem-cell-proliferation
#11
Patrick Narbonne, Paul S Maddox, Jean-Claude Labbé
Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS) and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C...
April 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28409689/effects-of-methoxychlor-on-igf-i-signaling-pathway-in-rat-ovary
#12
O Ozden-Akkaya, K Altunbas, A Yagcı
Follicular development and other ovarian functions are regulated by growth factors that can be affected by exogenous agents. Methoxychlor (MXC) is an organochloride pesticide that causes female infertility. We investigated how MXC affects the distribution of developing ovarian follicles in adult rats after treatment between embryonic day (E) 18 and postnatal day (PND) 7. We also measured insulin-like growth factor-I (IGF-I) and its receptor, IGF-IR, expressions in ovarian follicles and investigated whether MXC changed the levels of IGF-I and IGF-IR in the ovary...
2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28407669/metformin-inhibits-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-in-db-db-mice
#13
Shan Zhuang, Yongmei Jian, Yongning Sun
Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group)...
April 13, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28389653/identification-of-igf-1-enhanced-cytokine-expressions-targeted-by-mir-181d-in-glioblastomas-via-an-integrative-mirna-mrna-regulatory-network-analysis
#14
Kuo-Hao Ho, Peng-Hsu Chen, Edward Hsi, Chwen-Ming Shih, Wei-Chiao Chang, Chia-Hsiung Cheng, Cheng-Wei Lin, Ku-Chung Chen
The insulin-like growth factor (IGF)-1 signaling is relevant in regulating cell growth and cytokine secretions by glioblastomas. MicroRNAs determine the cell fate in glioblastomas. However, relationships between IGF-1 signaling and miRNAs in glioblastoma pathogenesis are still unclear. Our aim was to validate the IGF-1-mediated mRNA/miRNA regulatory network in glioblastomas. Using in silico analyses of mRNA array and RNA sequencing data from The Cancer Genome Atlas (TCGA), we identified 32 core enrichment genes that were highly associated with IGF-1-promoted cytokine-cytokine receptor interactions...
April 7, 2017: Scientific Reports
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
#15
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/28389416/cell-surface-grp78-facilitates-hepatoma-cells-proliferation-and-migration-by-activating-igf-ir
#16
Yancun Yin, Chen Chen, Jinliang Chen, Renhui Zhan, Qiang Zhang, Xiaoyan Xu, Defang Li, Minjing Li
The 78kDa glucose regulated protein (GRP78) is a multifunctional chaperone that is involved in a variety of cellular processes. Insulin like growth factor I receptor (IGF-IR) often aberrant expresses in many types of tumor cells. The IGF-IR signaling plays key roles in carcinogenesis and maintenance of the malignant phenotype. The crosstalk between GRP78 and IGF-IR molecules has not well been illuminated. Here, we demonstrated a reciprocal regulation of GRP78 expression and IGF-IR pathway activation. IGF-I induced GRP78 expression in hepatoma cells...
April 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28386360/neuroprotective-effect-of-mir-665-against-sevoflurane-anesthesia-induced-cognitive-dysfunction-in-rats-through-pi3k-akt-signaling-pathway-by-targeting-insulin-like-growth-factor-2
#17
Xihua Lu, Shuaiguo Lv, Yan Mi, Lei Wang, Gensheng Wang
The aim of this study was to investigate the in vivo and in vitro effects of miR-665 on sevoflurane anesthesia-induced cognitive dysfunction. SH-SY5Y cells and male SD rats were treated with sevoflurane to simulate anesthesia-induced cognitive dysfunction. The cells and rats both were transfected with a miR-665 mimic, inhibitor, scramble, IGF-2 siRNA, or treated with P13K/Akt inhibitor LY294002. The cell apoptosis, autophagy, growth related proteins, and mRNA levels were measured using different methods. The motor performance was assessed using the Morris water maze (MWM) test...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28383811/hsf1-phosphorylation-by-erk-gsk3-suppresses-rnf126-to-sustain-igf-iir-expression-for-hypertension-induced-cardiomyocyte-hypertrophy
#18
Chih-Yang Huang, Fa-Lun Lee, Shu-Fen Peng, Kuan-Ho Lin, Ray-Jade Chen, Tsung-Jung Ho, Fu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT1 R)...
April 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28382169/integration-of-receptor-tyrosine-kinases-determines-sensitivity-to-pi3k%C3%AE-selective-inhibitors-in-breast-cancer
#19
Yi-Chao Xu, Xiang Wang, Yi Chen, Si-Meng Chen, Xin-Ying Yang, Yi-Ming Sun, Mei-Yu Geng, Jian Ding, Ling-Hua Meng
PI3Kα-selective inhibitor BYL719 is currently in phase II/III clinical trial for the treatment of breast cancer, but highly variable response has been observed among patients. We sought to discover predictive biomarker for the efficacy of BYL719 by dissecting the proliferative signaling pathway mediated by PI3K in breast cancer. BYL719 concurrently inhibited the phosphorylation of AKT and ERK in PIK3CA-mutated human breast cancer cells. PI3K-regulated ERK phosphorylation was independent of canonical PDK1/AKT/mTOR pathway, while it was associated with RAF/MEK...
2017: Theranostics
https://www.readbyqxmd.com/read/28381504/insulin-receptor-substrate-signaling-controls-cardiac-energy-metabolism-and-heart-failure
#20
Cathy A Guo, Shaodong Guo
The heart is an insulin-dependent and energy consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth, and survival. Heart failure is highly associated with insulin resistance and heart failure patients suffer from the cardiac energy deficiency, structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics, and impairing cardiac contractility...
April 5, 2017: Journal of Endocrinology
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