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https://www.readbyqxmd.com/read/28330997/igfbp3-modulates-lung-tumorigenesis-and-cell-growth-through-igf1-signaling
#1
Yong A Wang, Yunguang Sun, Joshua D Palmer, Charalambos Solomides, Li-Ching Huang, Yu Shyr, Adam P Dicker, Bo Lu
Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether Igfbp3 deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade. To this end, an Igfbp3-null mouse model was generated in combination with KrasG12D to compare the tumor burden...
March 22, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28327432/feedback-from-arctic-charr-feed-flavour-stimulation-and-re-feeding-after-feed-deprivation-stimulate-genes-encoding-both-orexigenic-and-anorexigenic-neuropeptides
#2
Anja Striberny, Even H Jørgensen
Despite vast research attention, the knowledge about central mechanisms of appetite regulation in teleost remains inconclusive. A common strategy in studies on appetite regulating mechanisms is to measure the response to feed restriction or - deprivation, but responses vary between fish species and between experiments, and are also likely dependent on the degree of energy perturbation. The anadromous Arctic charr is an interesting model for studying appetite regulation as its feeding cycle comprises months of winter anorexia, and hyperphagia during summer...
March 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28324014/variation-in-the-insulin-like-growth-factor-1-gene-in-primates
#3
Peter Rotwein
Insulin-like growth factor 1 (IGF1) is a multifunctional peptide that is involved in a wide range of physiological and patho-physiological processes in many animal species, ranging from somatic growth in children to metabolism, and tissue regeneration and repair in adults. The IGF1 gene is under multifactorial regulation in the few species in which it has been studied, with major control being exerted by growth hormone (GH) through a gene expression pathway involving inducible binding of the STAT5b transcription factor to dispersed enhancer elements...
January 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323953/activation-of-male-liver-chromatin-accessibility-and-stat5-dependent-gene-transcription-by-plasma-growth-hormone-pulses
#4
Jeannette Connerney, Dana Lau-Corona, Andy Rampersaud, David J Waxman
Sex-differences in pituitary growth hormone (GH) secretion (pulsatile in males vs near continuous/persistent in females) impart sex-dependent expression to hundreds of genes in adult mouse liver. STAT5, a GH-activated transcription factor that is essential for liver sexual dimorphism, is dynamically activated in direct response to each male plasma GH pulse. However, the impact of GH-induced STAT5 pulses on liver chromatin accessibility and downstream transcriptional events is unknown. Here, we investigate the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later...
February 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323915/insulin-igf-1-and-gh-receptors-are-altered-in-an-adipose-tissue-depot-specific-manner-in-male-mice-with-modified-gh-action
#5
Rikke Hjortebjerg, Darlene E Berryman, Ross Comisford, Stuart J Frank, Edward O List, Mette Bjerre, Jan Frystyk, John J Kopchick
Growth hormone (GH) is an important determinant of glucose homeostasis and adipose tissue (AT) function. Using seven-month-old bovine GH transgenic (bGH) mice and GH receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression patterns of proteins involved in the interrelated signaling pathways of GH, insulin-like growth factor-1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice that may explain why GH effects depend on AT location...
February 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28316059/prevention-of-tumour-cell-apoptosis-associated-with-sustained-protein-kinase-b-phosphorylation-is-more-sensitive-to-regulation-by-insulin-signalling-than-stimulation-of-proliferation-and-extracellular-signal-regulated-kinase
#6
Christoph Schmid, Claudia Ghirlanda, Markus Niessen
Insulin controls blood glucose while insulin-like growth factor (IGF) 1 is an important growth factor. Interestingly, both hormones have overlapping bioactivities and can activate the same intracellular signal transduction cascades. Growth control (mainly by IGF1) and metabolic function (predominantly by insulin) are believed to depend on activation of extracellular signal-regulated kinases (ERKs) 1/2 and protein kinase B (Akt/PKB), respectively. Therefore, insulin analogues that are used to normalize blood glucose are tested for their ability to preferentially activate Akt/PKB but not ERK1/2 and mitogenesis...
March 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28315330/microrna-29-regulates-myocardial-microvascular-endothelial-cells-proliferation-and-migration-in-association-with-igf1-in-type-2-diabetes
#7
Zhenjie Li, Qingcai Yue, Haiying Peng
BACKGROUND: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. METHODS: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28296140/inhibitors-of-stat3-%C3%AE-catenin-and-igf-1r-sensitize%C3%A2-mouse-pik3ca%C3%A2-mutant%C3%A2-breast-cancer-to-pi3k-inhibitors
#8
Vanessa F Merino, Soonweng Cho, Xiaohui Liang, Sunju Park, Kideok Jin, Qian Chen, Duojia Pan, Cynthia A Zahnow, Alan R Rein, Saraswati Sukumar
Although mutations in the phosphoinositide 3-kinase-catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic mouse models expressing the human PIK3CA-H1047R and the -E545K hotspot mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cells lines derived from the PIK3CA tumors...
March 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28295976/insulin-like-growth-factor-1-deficiency-exacerbates-hypertension-induced-cerebral-microhemorrhages-in-mice-mimicking-the-aging-phenotype
#9
Stefano Tarantini, Noa M Valcarcel-Ares, Andriy Yabluchanskiy, Zsolt Springo, Gabor A Fulop, Nicole Ashpole, Tripti Gautam, Cory B Giles, Jonathan D Wren, William E Sonntag, Anna Csiszar, Zoltan Ungvari
Clinical and experimental studies show that aging exacerbates hypertension-induced cerebral microhemorrhages (CMHs), which progressively impair neuronal function. There is growing evidence that aging promotes insulin-like growth factor 1 (IGF-1) deficiency, which compromises multiple aspects of cerebromicrovascular and brain health. To determine the role of IGF-1 deficiency in the pathogenesis of CMHs, we induced hypertension in mice with liver-specific knockdown of IGF-1 (Igf1(f/f)  + TBG-Cre-AAV8) and control mice by angiotensin II plus l-NAME treatment...
March 14, 2017: Aging Cell
https://www.readbyqxmd.com/read/28286973/curcumin-inhibits-urothelial-tumor-development-by-suppressing-igf2-and-igf2-mediated-pi3k-akt-mtor-signaling-pathway
#10
Binqiang Tian, Yingmei Zhao, Tao Liang, Xuxiao Ye, Zuowei Li, Dongliang Yan, Qiang Fu, Yonghui Li
We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin...
March 11, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28277190/mir-422a-inhibits-glioma-proliferation-and-invasion-by-targeting-igf1-and-igf1r
#11
Haiyang Wang, Chongyang Tang, Meng Na, Wei Ma, Zhenfeng Jiang, Yifei Gu, Guizhen Ma, Haitao Ge, Hong Shen, Zhiguo Lin
Glioma is a common type of malignant brain tumor characterized by aggressive metastasis capability. Recent evidence has suggested that noncoding RNAs, including microRNAs, have important functions in the pathophysiology of glioma development. In this study, we investigated the biological function of miR-422a in human glioma. We found that miR-422a was downregulated in glioma tissues. We also demonstrated that expression of miR-422a in glioma cells markedly suppressed cell proliferation, migration, and invasion...
January 26, 2017: Oncology Research
https://www.readbyqxmd.com/read/28271457/insulin-growth-factor-1-correlates-with-higher-bone-mineral-density-and-lower-inflammation-status-in-obese-adult-subjects
#12
Rachele Fornari, Chiara Marocco, Davide Francomano, Simona Fittipaldi, Carla Lubrano, Viviana M Bimonte, Lorenzo M Donini, Emanuele Nicolai, Antonio Aversa, Andrea Lenzi, Emanuela A Greco, Silvia Migliaccio
PURPOSE: Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals...
March 7, 2017: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28265342/integrating-insulin-like-growth-factor-1-and-sex-hormones-into-neuroprotection-implications-for-diabetes
#13
REVIEW
Jacob Huffman, Christina Hoffmann, George T Taylor
Brain integrity and cognitive aptitude are often impaired in patients with diabetes mellitus, presumably a result of the metabolic complications inherent to the disease. However, an increasing body of evidence has demonstrated the central role of insulin-like growth factor 1 (IGF1) and its relation to sex hormones in many neuroprotective processes. Both male and female patients with diabetes display abnormal IGF1 and sex-hormone levels but the comparison of these fluctuations is seldom a topic of interest. It is interesting to note that both IGF1 and sex hormones have the ability to regulate phosphoinositide 3-kinase-Akt and mitogen-activated protein kinases-extracellular signal-related kinase signaling cascades in animal and cell culture models of neuroprotection...
February 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28260872/reduced-nuclear-translocation-of-serum-response-factor-is-associated-with-skeletal-muscle-atrophy-in-a-cigarette-smoke-induced-mouse-model-of-copd
#14
Ran Ma, Xuefang Gong, Hua Jiang, Chunyi Lin, Yuqin Chen, Xiaoming Xu, Chenting Zhang, Jian Wang, Wenju Lu, Nanshan Zhong
Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanism remains elusive. Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth. In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28258923/cancer-associated-fibroblasts-promote-irradiated-cancer-cell-recovery-through-autophagy
#15
Yongbin Wang, Guifang Gan, Bocheng Wang, Jinliang Wu, Yuan Cao, Dan Zhu, Yan Xu, Xiaona Wang, Hongxiu Han, Xiaoling Li, Ming Ye, Jiangmin Zhao, Jun Mi
Tumor relapse after radiotherapy is a significant challenge to oncologists, even after recent the advances in technologies. Here, we showed that cancer-associated fibroblasts (CAFs), a major component of cancer stromal cells, promoted irradiated cancer cell recovery and tumor relapse after radiotherapy. We provided evidence that CAFs-produced IGF1/2, CXCL12 and β-hydroxybutyrate were capable of inducing autophagy in cancer cells post-radiation and promoting cancer cell recovery from radiation-induced damage in vitro and in vivo in mice...
February 22, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28257443/analysis-of-large-versus-small-dogs-reveals-three-genes-on-the-canine-x-chromosome-associated-with-body-weight-muscling-and-back-fat-thickness
#16
Jocelyn Plassais, Maud Rimbault, Falina J Williams, Brian W Davis, Jeffrey J Schoenebeck, Elaine A Ostrander
Domestic dog breeds display significant diversity in both body mass and skeletal size, resulting from intensive selective pressure during the formation and maintenance of modern breeds. While previous studies focused on the identification of alleles that contribute to small skeletal size, little is known about the underlying genetics controlling large size. We first performed a genome-wide association study (GWAS) using the Illumina Canine HD 170,000 single nucleotide polymorphism (SNP) array which compared 165 large-breed dogs from 19 breeds (defined as having a Standard Breed Weight (SBW) >41 kg [90 lb]) to 690 dogs from 69 small breeds (SBW ≤41 kg)...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28250234/apelin-apln-regulates-progesterone-secretion-and-oocyte-maturation-in-bovine-ovarian-cells
#17
Jennifer Roche, Christelle Ramé, Maxime Reverchon, Namya Mellouk, Agnieska Rak, Pascal Froment, Joëlle Dupont
APLN and its G-protein coupled receptor APLNR are expressed in the bovine ovary. However, their role in granulosa cells and oocytes is unknown. Here, we studied their expression in bovine ovarian cells and investigated their regulation in cultured luteinizing granulosa cells in response to IGF1 and FSH. We determined the effect and the molecular mechanism of APLN (isoforms 17 and 13) on bovine granulosa cell progesterone secretion and on oocyte maturation. By RT-qPCR and immunoblot, we showed that the expression of both APLN and APLNR in granulosa and oocytes significantly increased with ovarian follicles size whereas it was similar in theca interstitial cells...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28249788/the-mrna-expression-of-insulin-like-growth-factor-1-igf1-is-decreased-in-the-rat-frontal-cortex-following-gamma-hydroxybutyrate-ghb-administration
#18
Erika Brolin, Jenny Johansson, Sofia Zelleroth, Shanti Diwakarla, Fred Nyberg, Alfhild Grönbladh, Mathias Hallberg
In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function...
February 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28249168/autocrine-igf1-signaling-mediates-pancreatic-tumor-cell-dormancy-in-the-absence-of-oncogenic-drivers
#19
Nirakar Rajbhandari, Wan-Chi Lin, Barbara L Wehde, Aleata A Triplett, Kay-Uwe Wagner
Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. Although tumor growth and homeostasis are largely dependent on these oncogenes, a few residual cancer cells are able to survive the ablation of mutant KRAS and c-MYC. By performing a genome-wide gene expression analysis of in vivo-derived bulk tumor cells and residual cancer cells lacking the expression of mutant KRAS or c-MYC, we have identified an increase in autocrine IGF1/AKT signaling as a common survival mechanism in dormant cancer cells...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28244645/obesity-and-metabolic-dysfunction-severely-influence-prostate-cell-function-role-of-insulin-and-igf1
#20
Fernando L-López, André Sarmento-Cabral, Vicente Herrero-Aguayo, Manuel D Gahete, Justo P Castaño, Raúl M Luque
Obesity is a major health problem that courses with severe comorbidities and a drastic impairment of homeostasis and function of several organs, including the prostate gland (PG). The endocrine-metabolic regulatory axis comprising growth hormone (GH), insulin and IGF1, which is drastically altered under extreme metabolic conditions such as obesity, also plays relevant roles in the development, modulation and homeostasis of the PG. However, its implication in the pathophysiological interplay between obesity and prostate function is still to be elucidated...
February 28, 2017: Journal of Cellular and Molecular Medicine
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