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https://www.readbyqxmd.com/read/28544360/impairment-of-insulin-signalling-in-peripheral-tissue-fails-to-extend-murine-lifespan
#1
Troy L Merry, Doreen Kuhlow, Beate Laube, Doris Pöhlmann, Andreas F H Pfeiffer, C Ronald Kahn, Michael Ristow, Kim Zarse
Impaired insulin/IGF1 signalling has been shown to extend lifespan in model organisms ranging from yeast to mammals. Here we sought to determine the effect of targeted disruption of the insulin receptor (IR) in non-neuronal tissues of adult mice on the lifespan. We induced hemizygous (PerIRKO(+/-) ) or homozygous (PerIRKO(-/-) ) disruption of the IR in peripheral tissue of 15-weeks-old mice using a tamoxifen-inducible Cre transgenic mouse with only peripheral tissue expression, and subsequently monitored glucose metabolism, insulin signalling and spontaneous death rates over 4 years...
May 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/28539837/ezh2-acts-as-a-tumor-suppressor-in-kras-driven-lung-adenocarcinoma
#2
Yanxiao Wang, Ning Hou, Xuan Cheng, Jishuai Zhang, Xiaohong Tan, Chong Zhang, Yuling Tang, Yan Teng, Xiao Yang
Previous studies have suggested that enhancer zeste homolog 2 (Ezh2), a histone methyltransferase subunit of polycomb repressive complex 2 (PRC2), acts as an oncogene in lung adenocarcinoma (ADC) development. However, we found that in human lung ADC samples, deletion and mutations of EZH2 were also frequently present, with 14% of patients harboring loss-of-function EZH2 alterations. To explore the effect of Ezh2 loss on lung tumor formation, lung epithelial Ezh2 gene was deleted in Kras-driven lung ADC mouse model...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#3
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/28533420/igf1-stimulates-greater-muscle-hypertrophy-in-the-absence-of-myostatin-in-male-mice
#4
Alexander Hennebry, Jenny M Oldham, Tea Shavlakadze, Miranda Grounds, Philip Sheard, Marta Fiorotto, Shelley J Falconer, Heather K Smith, Carole Berry, Ferenc Jeanplong, Jeremy Bracegirdle, Kenneth G Matthews, Gina Nicholas, Monica Senna-Salerno, Trevor Watson, Christopher D McMahon
Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null (Mstn-/-) mice with mice over-expressing Igf1 in skeletal muscle (Igf1+) to generate six genotypes of male mice; wild-type (Mstn+/+), Mstn+/-, Mstn-/-, Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+...
May 22, 2017: Journal of Endocrinology
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
#5
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
#6
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/28494512/gene-expression-profiling-of-skeletal-muscle-after-volumetric-muscle-loss
#7
Kristo Nuutila, Dharaniya Sakthivel, Carla Kruse, Peter Tran, Giorgio Giatsidis, Indranil Sinha
Volumetric muscle loss (VML), usually occurring following traumatic injury, results in a composite loss of muscle mass. These injuries manifest as decreased strength and functional impairments. Clinically, these injuries often heal with fibrosis, as opposed to skeletal muscle regeneration. The present study examines the healing patterns of a skeletal muscle following VML in a murine model. Eight-week old male C57BL/6J mice used in the study underwent either bilateral VML injury or cryoinjury, a widely-used model known to induce skeletal muscle regeneration...
May 11, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28479388/acceleration-based-training-a-new-mode-of-training-in-senescent-rats-improving-performance-and-left-ventricular-and-muscle-functions
#8
Thierry Launay, Iman Momken, Serge Carreira, Nathalie Mougenot, Xian-Long Zhou, Leanne De Koning, Romain Niel, Bruno Riou, Véronique Billat, Sophie Besse
High intensity training (HIT) has been shown to improve maximal aerobic capacity and muscle protein synthesis but has not yet been investigated in senescent rats. We hypothesized that the change of speed (acceleration) during each bout of HIT acts as a stimulus responsible for the adaptations of the organism to exercise. Twenty two month-old (mo) rats (n=14) were subjected to a short acceleration protocol (20-30min) of exercise, comprising 3 independent bouts of acceleration and compared to an age-matched sedentary group (n=14)...
May 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28476321/murine-model-and-mechanisms-of-treatment-induced-painful-diabetic-neuropathy
#9
Juliet M Nicodemus, Cynthia Enriquez, Alexandra Marquez, Carlos J Anaya, Corinne G Jolivalt
Diabetes mellitus represents a group of metabolic diseases that are characterized by hyperglycemia caused by either lack of insulin production or a reduced ability to respond to insulin. It is estimated that there were 347 million people worldwide who suffered from diabetes in 2008 and incidence is predicted to double by 2050. Neuropathy is the most common complication of long-term diabetes and approximately 30% of these subjects develop chronic neuropathic pain. A distinct acute, severe form of neuropathic pain, called insulin neuritis or treatment-induced painful neuropathy of diabetes (TIND), may also occur shortly after initiation of intensive glycemic control, with an incidence rate of up to 10...
May 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28474535/long-term-propagation-of-porcine-undifferentiated-spermatogonia
#10
Pengfei Zhang, Xiaoxu Chen, Yi Zheng, Jinsheng Zhu, Yuwei Qin, Yinghua Lv, Wenxian Zeng
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis and fertility throughout the adult life of a male. Genetic manipulations of SSCs combined with germ cell transplantation present a novel approach for gene therapy and production of genetically modified animals. However, the rarity of SSCs within mammalian testes remains an impediment to related applications that require sufficient numbers of SSCs, making in vitro expansion of SSCs a prerequisite. Nevertheless, long-term culture systems of SSCs from large animals have not been established yet...
May 5, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28474384/exploring-genetic-susceptibility-to-obesity-through-genome-functional-pathway-analysis
#11
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...
June 2017: Obesity
https://www.readbyqxmd.com/read/28472963/experimental-approach-to-igf-1-therapy-in-ccl4-induced-acute-liver-damage-in-healthy-controls-and-mice-with-partial-igf-1-deficiency
#12
Luis A Morales-Garza, Juan E Puche, Gabriel A Aguirre, Úrsula Muñoz, Mariano García-Magariño, Rocío G De la Garza, Inma Castilla-Cortazar
BACKGROUND: Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl4)-induced liver damage compared to healthy controls (Wt Igf (+/+)). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 (+/-))...
May 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#13
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/28471324/the-structure-function-relationships-of-insulin-like-growth-factor-1-ec-in-c2c12-cells
#14
Qian Yi, Jianguo Feng, Ling He, Rongxue Wan, Hui Zeng, Li Yang, Shiyong Wu, Liling Tang
Insulin-like growth factor 1 (IGF1) is a crucial growth factor, that regulates skeletal muscles development during cell growth and repair. Recently, its alternative splicing variant, named IGF1Ec, also named mechano-growth factor (MGF), has gained attentions as a new damage repair factor. However, the structure-function relationships of IGF1Ec have not been fully clarified due to contradictory reports. In this study, we systematically investigated physiologic responses of C2C12 muscle cells to IGF1Ec, IGF1 and MGF E peptide...
May 4, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28467045/assuring-consistent-performance-of-an-insulin-like-growth-factor-1-maldimmunoassay-by-monitoring-measurement-quality-indicators
#15
Frank Klont, Nick H T Ten Hacken, Péter Horvatovich, Stephan J L Bakker, Rainer Bischoff
Analytical methods based on mass spectrometry (MS) have been successfully applied in biomarker discovery studies, while the role of MS in translating biomarker candidates to clinical diagnostics is less pronounced. MALDImmunoassays-methods that combine immunoaffinity enrichment with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric detection-are attractive analytical approaches for large-scale sample analysis by virtue of their ease of operation and high-throughput capabilities...
May 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28462703/divergent-roles-of-irs-insulin-receptor-substrate-1-and-2-in-liver-and-skeletal-muscle
#16
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/28462077/pdk1-foxo1-pathway-in-agrp-neurons-of-arcuate-nucleus-promotes-bone-formation-via-ghrh-gh-igf1-axis
#17
Hideyuki Sasanuma, Masanori Nakata, Kumari Parmila, Jun Nakae, Toshihiko Yada
OBJECTIVE: In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis, functions connected to bone metabolism. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) serves as a major signaling molecule particularly for leptin and insulin in AgRP neurons. We asked whether PDK1 in AGRP neurons also contributes to bone metabolism. METHODS: We generated AgRP neuron-specific PDK1 knockout (Agrp Pdk1(-/-) ) mice and those with additional AgRP neuron-specific expression of transactivation-defective FoxO1 (Agrp Pdk1(-/-)Δ256Foxo1)...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#18
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
#19
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
#20
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
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