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https://www.readbyqxmd.com/read/28630896/the-gh-receptor-exon-3-deletion-is-a-marker-of-male-specific-exceptional-longevity-associated-with-increased-gh-sensitivity-and-taller-stature
#1
Danny Ben-Avraham, Diddahally R Govindaraju, Temuri Budagov, Delphine Fradin, Peter Durda, Bing Liu, Sandy Ott, Danielle Gutman, Lital Sharvit, Robert Kaplan, Pierre Bougnères, Alex Reiner, Alan R Shuldiner, Pinchas Cohen, Nir Barzilai, Gil Atzmon
Although both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling were shown to regulate life span in lower organisms, the role of GH signaling in human longevity remains unclear. Because a GH receptor exon 3 deletion (d3-GHR) appears to modulate GH sensitivity in humans, we hypothesized that this polymorphism could play a role in human longevity. We report a linear increased prevalence of d3-GHR homozygosity with age in four independent cohorts of long-lived individuals: 841 participants [567 of the Longevity Genes Project (LGP) (8% increase; P = 0...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28629210/activation-of-igf-i-survival-signaling-and-its-compensative-inhibition-of-the-cardiac-apoptosis-on-carotid-arteries-balloon-injured-rat-hearts
#2
Cheng-Hong Hsieh, Peiying Pai, Jia-Ping Wu, Tsung-Jung Ho, Chieh-Hsi Wu, Marthandam Asokan Shibu, Cecilia Hsuan Day, Vijaya Padma Viswanadha, Ho-Lin Chuang, Chih-Yang Huang
In this study, a rat carotid balloon injury-animal model was used to elucidate the temporal relation of hypertrophy in the progression of cardiac damage and the role of IGF-I survival pathway on course of the cardiac damage. Rats were subjected to carotid balloon-injury and examined at different time points. We further studied the heart-weight/body-weight-ratio, histology and protein expression to understand the pathological events associated with percutaneous transluminal coronary angioplasty (PTCA) induced damages...
June 30, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/28627605/mesenchymal-stem-cells-promote-endothelial-progenitor-cell-proliferation-by-secreting-insulin%C3%A2-like-growth-factor%C3%A2-1
#3
Jixue Hou, Xinyu Peng, Jing Wang, Hongwei Zhang, Jie Xia, Quanhu Ge, Xiaoyi Wang, Xueling Chen, Xiangwei Wu
Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) interact with each other. EPCs are able to promote the self‑renewal of MSCs as niche cells in murine bone marrow, and MSCs are able to promote EPC proliferation in vitro in a co‑culture system. It has previously been reported that MSCs can secrete insulin‑like growth factor‑1 (IGF‑1), which serves critical functions in EPC proliferation. However, the mechanism underlying the IGF‑1‑mediated proliferation of EPCs remains unclear...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624391/efficacy-of-melatonin-il-25-and-siil-17b-in-tumorigenesis-associated-properties-of-breast-cancer-cell-lines
#4
Gabriela Bottaro Gelaleti, Thaiz Ferraz Borin, Larissa Bazela Maschio-Signorini, Marina Gobbe Moschetta, Bruna Victorasso Jardim-Perassi, Guilherme Berto Calvinho, Mariana Castilho Facchini, Alicia M Viloria-Petit, Debora Aparecida Pires de Campos Zuccari
Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells...
June 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28621713/gpe-promotes-the-proliferation-and-migration-of-mouse-embryonic-neural-stem-cells-and-their-progeny-in-vitro
#5
Cristina Almengló, Pablo Devesa, Jesús Devesa, Víctor M Arce
This study was designed to investigate a possible role of the N-terminal tripeptide of insulin-like growth factor-1 (IGF-I), Gly-Pro-Glu (GPE), physiologically generated in neurons following IGF-I-specific cleavage, in promoting neural regeneration after an injury. Primary cultures of mouse neural stem cells (NSCs), obtained from 13.5 Days post-conception (dpc) mouse embryos, were challenged with either GPE, growth hormone (GH), or GPE + GH and the effects on cell proliferation, migration, and survival were evaluated both under basal conditions and in response to a wound healing assay...
June 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#6
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28619606/pivotal-roles-of-glycogen-synthase-3-in-hepatocellular-carcinoma
#7
REVIEW
Melchiorre Cervello, Giuseppa Augello, Antonella Cusimano, Maria Rita Emma, Daniele Balasus, Antonina Azzolina, James A McCubrey, Giuseppe Montalto
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and represents the second most frequently cancer and third most common cause of death from cancer worldwide. At advanced stage, HCC is a highly aggressive tumor with a poor prognosis and with very limited response to common therapies. Therefore, there is still the need for new effective and well-tolerated therapeutic strategies. Molecular-targeted therapies hold promise for HCC treatment. One promising molecular target is the multifunctional serine/threonine kinase glycogen synthase kinase 3 (GSK-3)...
June 6, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28617951/altered-expression-of-igf-i-system-in-neurons-of-the-inflamed-spinal-cord-during-acute-experimental-autoimmune-encephalomyelitis
#8
Azita Parvaneh Tafreshi, Farideh Talebi, Samira Ghorbani, Claude Bernard, Farshid Noorbakhsh
BACKGROUND: There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. OBJECTIVES: In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. METHODS: To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling...
June 15, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28610907/insulin-like-growth-factor-igf-like-peptide-and-20-hydroxyecdysone-regulate-the-growth-and-development-of-the-male-genital-disk-through-different-mechanisms-in-the-silkmoth-bombyx-mori
#9
Daiki Fujinaga, Yusuke Kohmura, Naoki Okamoto, Hiroshi Kataoka, Akira Mizoguchi
It is well established that ecdysteroids play pivotal roles in the regulation of insect molting and metamorphosis. However, the mechanisms by which ecdysteroids regulate the growth and development of adult organs after pupation are poorly understood. Recently, we have identified insulin-like growth factor (IGF)-like peptides (IGFLPs), which are secreted after pupation under the control of 20-hydroxyecdysone (20E). In the silkmoth, Bombyx mori, massive amounts of Bombyx-IGFLP (BIGFLP) are present in the hemolymph during pupal-adult development, suggesting its importance in the regulation of adult tissue growth...
June 10, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28608366/complement-component-1-q-subcomponent-binding-protein-c1qbp-in-lipid-rafts-mediates-hepatic-metastasis-of-pancreatic-cancer-by-regulating-igf-1-igf-1r-signaling
#10
Haojun Shi, Winston Fang, Minda Liu, Deliang Fu
Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown...
June 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28607354/igf-1-mediated-neurogenesis-involves-a-novel-rit1-akt-sox2-cascade
#11
Sajad Mir, Weikang Cai, Shaun W Carlson, Kathryn E Saatman, Douglas A Andres
Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601906/unravelling-the-regulation-of-insulin-transport-across-the-brain-endothelial-cell
#12
Sarah M Gray, Kevin W Aylor, Eugene J Barrett
AIMS/HYPOTHESIS: For circulating insulin to act on the brain it must cross the blood-brain barrier (BBB). Remarkably little is known about how circulating insulin crosses the BBB's highly restrictive brain endothelial cells (BECs). Therefore, we examined potential mechanisms regulating BEC insulin uptake, signalling and degradation during BEC transcytosis, and how transport is affected by a high-fat diet (HFD) and by astrocyte activity. METHODS: (125)I-TyrA14-insulin uptake and transcytosis, and the effects of insulin receptor (IR) blockade, inhibition of insulin signalling, astrocyte stimulation and an HFD were tested using purified isolated BECs (iBECs) in monoculture and co-cultured with astrocytes...
June 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28595357/the-alzheimer-s-disease-transcriptome-mimics-the-neuroprotective-signature-of-igf-1-receptor-deficient-neurons
#13
Caroline George, Géraldine Gontier, Philippe Lacube, Jean-Christophe François, Martin Holzenberger, Saba Aïd
Seminal studies using post-mortem brains of patients with Alzheimer's disease evidenced aberrant insulin-like growth factor 1 receptor (IGF1R) signalling. Addressing causality, work in animal models recently demonstrated that long-term suppression of IGF1R signalling alleviates Alzheimer's disease progression and promotes neuroprotection. However, the underlying mechanisms remain largely elusive. Here, we showed that genetically ablating IGF1R in neurons of the ageing brain efficiently protects from neuroinflammation, anxiety and memory impairments induced by intracerebroventricular injection of amyloid-β oligomers...
June 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28592272/betaine-promotes-cell-differentiation-of-human-osteoblasts-in-primary-culture
#14
Isabella Villa, Pamela Senesi, Anna Montesano, Anita Ferraretto, Fernanda Vacante, Alice Spinello, Michela Bottani, Simona Bolamperti, Alessandro Rubinacci, Livio Luzi, Ileana Terruzzi
BACKGROUND: Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation. METHODS: The effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery...
June 7, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28591735/discoidin-domain-receptor-1-modulates-insulin-receptor-signaling-and-biological-responses-in-breast-cancer-cells
#15
Veronica Vella, Roberta Malaguarnera, Maria Luisa Nicolosi, Chiara Palladino, Cristina Spoleti, Michele Massimino, Paolo Vigneri, Michele Purrello, Marco Ragusa, Andrea Morrione, Antonino Belfiore
The fetal isoform A of the insulin receptor (IR-A) is frequently overexpressed in a variety of malignancies including breast cancer. IR overexpression has a recognized role in cancer progression and resistance to anticancer therapies. In particular, IR-A has a peculiar mitogenic potential and is activated not only by insulin but also by IGF-2. Previously, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591635/hypothalamic-pituitary-axis-regulates-hydrogen-sulfide-production
#16
Christopher Hine, Hyo-Jeong Kim, Yan Zhu, Eylul Harputlugil, Alban Longchamp, Marina Souza Matos, Preeti Ramadoss, Kevin Bauerle, Lear Brace, John M Asara, C Keith Ozaki, Sheue-Yann Cheng, Subhankar Singha, Kyo Han Ahn, Alec Kimmelman, Ffolliott M Fisher, Pavlos Pissios, Dominic J Withers, Colin Selman, Rui Wang, Kelvin Yen, Valter D Longo, Pinchas Cohen, Andrzej Bartke, John J Kopchick, Richard Miller, Anthony N Hollenberg, James R Mitchell
Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (H2S) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries. Here we found increased hepatic H2S production in long-lived mouse strains of reduced GH and/or TH action, and in a cell-autonomous manner upon serum withdrawal in vitro...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28587338/mediation-of-insulin-growth-factor-1-in-alzheimer-s-disease-and-the-mechanism-of-prnp-genetic-expression-and-the-pi3k-akt-signaling-pathway
#17
Guohong Jiang, Changming Wang, Jun Zhang, Haijun Liu
The aim of the study was to examine the mediation of insulin growth factor-1 (IGF-1) in Alzheimer's disease (AD), as well as the underlying mechanism of the PRNP genetic expression and PI3K/Akt signaling pathway. The Aβ25-35-incubated rat adrenal pheochromocytoma cell (PC12) in vitro was established, constituting the AD model. Different doses (0, 20, 40 and 80 ng/ml) of IGF-1 were used in PC12 cells and the level of PRNP mRNA was tested after 24 h using the quantitative PCR method and the level of APP protein was assessed using western blot analysis...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28583713/igf-1r-signalling-contributes-to-il-6-production-and-t-cell-dependent-inflammation-in-rheumatoid-arthritis
#18
Malin C Erlandsson, Sofia Töyrä Silfverswärd, Mitra Nadali, Minna Turkkila, Mattias N D Svensson, Ing-Marie Jonsson, Karin M E Andersson, Maria I Bokarewa
BACKGROUND: Signalling through insulin-like growth factor 1 receptor (IGF-1R) is essential for cell survival, but may turn pathogenic in uncontrolled tissue growth in tumours. In rheumatoid arthritis (RA), the IGF-1R signalling is activated and supports expansion of the inflamed synovia. AIM: In the present study, we assess if disruption of IGF-1R signalling resolves arthritis. MATERIAL AND METHODS: Clinical associations of IGF-1R expression in leukocytes of the peripheral blood were studied in 84 RA patients...
June 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28581517/functional-antagonism-of-%C3%AE-arrestin-isoforms-balance-igf-1r-expression-and-signalling-with-distinct-cancer-related-biological-outcomes
#19
N Suleymanova, C Crudden, T Shibano, C Worrall, I Oprea, A Tica, G A Calin, A Girnita, L Girnita
With very similar 3D structures, the widely expressed β-arrestin isoforms 1 and 2 play at times identical, distinct or even opposing roles in regulating various aspects of G protein-coupled receptors (GPCR) expression and signalling. Recent evidence recognizes the β-arrestin system as a key regulator of not only GPCRs, but also receptor tyrosine kinases, including the highly cancer relevant insulin-like growth factor type 1 receptor (IGF-1R). Binding of β-arrestin1 to IGF-1R leads to ligand-dependent degradation of the receptor and generates additional MAPK/ERK signalling, protecting cancer cells against anti-IGF-1R therapy...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28580287/insulin-controls-food-intake-and-energy-balance-via-npy-neurons
#20
Kim Loh, Lei Zhang, Amanda Brandon, Qiaoping Wang, Denovan Begg, Yue Qi, Melissa Fu, Rishikesh Kulkarni, Jonathan Teo, Paul Baldock, Jens C Brüning, Gregory Cooney, Greg Neely, Herbert Herzog
OBJECTIVES: Insulin signaling in the brain has been implicated in the control of satiety, glucose homeostasis and energy balance. However, insulin signaling is dispensable in energy homeostasis controlling AgRP or POMC neurons and it is unclear which other neurons regulate these effects. Here we describe an ancient insulin/NPY neuronal network that governs energy homeostasis across phyla. METHODS: To address the role of insulin action specifically in NPY neurons, we generated a variety of models by selectively removing insulin signaling in NPY neurons in flies and mice and testing the consequences on energy homeostasis...
June 2017: Molecular Metabolism
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