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https://www.readbyqxmd.com/read/27930690/structural-mapping-and-functional-characterization-of-zebrafish-class-b-g-protein-coupled-receptor-gpcr-with-dual-ligand-selectivity-towards-glp-1-and-glucagon
#1
Deena A Oren, Yang Wei, Luce Skrabanek, Billy K C Chow, Thomas Mommsen, Svetlana Mojsov
GLP-1 and glucagon regulate glucose metabolism through a network of metabolic pathways initiated upon binding to their specific receptors that belong to class B G-protein coupled receptors (GPCRs). The therapeutic potential of glucagon is currently being evaluated, while GLP-1 is already used in the treatment of type 2 diabetes and obesity. Development of a second generation of GLP-1 based therapeutics depends on a molecular and structural understanding of the interactions between the GLP-1 receptor (GLP-1R) and its ligand GLP-1...
2016: PloS One
https://www.readbyqxmd.com/read/27916275/artemisinins-target-gabaa-receptor-signaling-and-impair-%C3%AE-cell-identity
#2
Jin Li, Tamara Casteels, Thomas Frogne, Camilla Ingvorsen, Christian Honoré, Monica Courtney, Kilian V M Huber, Nicole Schmitner, Robin A Kimmel, Roman A Romanov, Caterina Sturtzel, Charles-Hugues Lardeau, Johanna Klughammer, Matthias Farlik, Sara Sdelci, Andhira Vieira, Fabio Avolio, François Briand, Igor Baburin, Peter Májek, Florian M Pauler, Thomas Penz, Alexey Stukalov, Manuela Gridling, Katja Parapatics, Charlotte Barbieux, Ekaterine Berishvili, Andreas Spittler, Jacques Colinge, Keiryn L Bennett, Steffen Hering, Thierry Sulpice, Christoph Bock, Martin Distel, Tibor Harkany, Dirk Meyer, Giulio Superti-Furga, Patrick Collombat, Jacob Hecksher-Sørensen, Stefan Kubicek
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm...
November 30, 2016: Cell
https://www.readbyqxmd.com/read/27877088/aloe-emodin-suppresses-hypoxia-induced-retinal-angiogenesis-via-inhibition-of-hif-1%C3%AE-vegf-pathway
#3
Jianming Wu, Xiao Ke, Wei Wang, Hongcheng Zhang, Na Ma, Wei Fu, Manxi Zhao, Xiaoping Gao, Xiaofeng Hao, Zhirong Zhang
Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. Methods: We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl2 to the ARPE-19 cells, then treated the cells with different concentrations of AE (0...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27849017/elmo1-protects-renal-structure-and-ultrafiltration-in-kidney-development-and-under-diabetic-conditions
#4
Krishna Rakesh Sharma, Karl Heckler, Sandra J Stoll, Jan-Luuk Hillebrands, Katharina Kynast, Esther Herpel, Stefan Porubsky, Marlies Elger, Boris Hadaschik, Karen Bieback, Hans-Peter Hammes, Peter P Nawroth, Jens Kroll
Engulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#5
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian, Jeff S Mumm
The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed 'ARQiv-HTS'. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27818940/critical-role-for-adenosine-receptor-a2a-in-%C3%AE-cell-proliferation
#6
Nadja Schulz, Ka-Cheuk Liu, Jérémie Charbord, Charlotte L Mattsson, Lingjie Tao, Dominika Tworus, Olov Andersson
OBJECTIVE: Pharmacological activation of adenosine signaling has been shown to increase β-cell proliferation and thereby β-cell regeneration in zebrafish and rodent models of diabetes. However, whether adenosine has an endogenous role in regulating β-cell proliferation is unknown. The objective of this study was to determine whether endogenous adenosine regulates β-cell proliferation-either in the basal state or states of increased demand for insulin-and to delineate the mechanisms involved...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27810111/embryonic-exposures-to-perfluorooctanesulfonic-acid-pfos-disrupt-pancreatic-organogenesis-in-the-zebrafish-danio-rerio
#7
Karilyn E Sant, Haydee M Jacobs, Katrina A Borofski, Jennifer B Moss, Alicia R Timme-Laragy
Perfluorooctanesulfonic acid (PFOS) is a ubiquitous environmental contaminant, previously utilized as a non-stick application for consumer products and firefighting foam. It can cross the placenta, and has been repeatedly associated with increased risk for diabetes in epidemiological studies. Here, we sought to establish the hazard posed by embryonic PFOS exposures on the developing pancreas in a model vertebrate embryo, and develop criteria for an adverse outcome pathway (AOP) framework to study the developmental origins of metabolic dysfunction...
January 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27802896/expression-of-adenosine-receptors-and-vegf-during-angiogenesis-and-its-inhibition-by-pentoxifylline-a-study-using-zebrafish-model
#8
Jhansi Rani Nathan, Ganesh Lakshmanan, Felicia Mary Michael, Prakash Seppan, Malathi Ragunathan
Angiogenesis, formation of new blood vessels is an important process involved in neovascular diseases and tumor progression. Understanding and defining novel therapeutic targets of neovascular diseases like retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration have been hindered by a lack of appropriate animal models. Zebrafish provides an excellent vertebrate model to study above disorders since its circulatory system and retinal layers are similar to mammals. Adenosine is a known mediator of angiogenesis in hypoxic condition and adenosine receptor antagonists such as theophylline, theobromine are known to exert antiangiogenic properties...
October 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27696252/chronic-hyperglycemia-affects-bone-metabolism-in-adult-zebrafish-scale-model
#9
Marta Carnovali, Livio Luzi, Giuseppe Banfi, Massimo Mariotti
Type II diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia that induce other pathologies including diabetic retinopathy and bone disease. The mechanisms implicated in bone alterations induced by type II diabetes mellitus have been debated for years and are not yet clear because there are other factors involved that hide bone mineral density alterations. Despite this, it is well known that chronic hyperglycemia affects bone health causing fragility, mechanical strength reduction and increased propensity of fractures because of impaired bone matrix microstructure and aberrant bone cells function...
October 1, 2016: Endocrine
https://www.readbyqxmd.com/read/27690380/flavonoids-from-litsea-japonica-inhibit-ages-formation-and-rat-lense-aldose-reductase-in-vitro-and-vessel-dilation-in-zebrafish
#10
Ik-Soo Lee, Yu Jin Kim, Seung-Hyun Jung, Joo-Hwan Kim, Jin Sook Kim
In our ongoing efforts to identify effective naturally sourced agents for the treating of diabetic complications, two new (1 and 2) and 11 known phenolic compounds (3-13) were isolated from an 80 % ethanol extract of Litsea japonica leaves. The structures of the new compounds were established by spectroscopic and chemical studies. These isolates (1-13) were subjected to an in vitro bioassay evaluating their inhibitory activity on advanced glycation end products formation and rat lens aldose reductase activity...
September 30, 2016: Planta Medica
https://www.readbyqxmd.com/read/27531950/cin85-deficiency-prevents-nephrin-endocytosis-and-proteinuria-in-diabetes
#11
Beina Teng, Patricia Schroder, Janina Müller-Deile, Heiko Schenk, Lynne Staggs, Irini Tossidou, Ivan Dikic, Hermann Haller, Mario Schiffer
Diabetic nephropathy (DN) is the major cause of end stage renal disease worldwide. Podocytes are important for glomerular filtration barrier function and maintenance of size selectivity in protein filtration in the kidney. Podocyte damage is the basis of many glomerular diseases characterized by loss of interdigitating foot processes and decreased expression of components of the slit diaphragm. Nephrin, a podocyte specific protein, is the main component of the slit diaphragm. Loss of nephrin is observed in human and rodent models of diabetic kidney disease...
August 16, 2016: Diabetes
https://www.readbyqxmd.com/read/27516442/igfbp1-increases-%C3%AE-cell-regeneration-by-promoting-%C3%AE-to-%C3%AE-cell-transdifferentiation
#12
Jing Lu, Ka-Cheuk Liu, Nadja Schulz, Christos Karampelias, Jérémie Charbord, Agneta Hilding, Linn Rautio, Philippe Bertolino, Claes-Göran Östenson, Kerstin Brismar, Olov Andersson
There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole-genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β-cell regeneration. We then tested the proteins' ability to potentiate β-cell regeneration in zebrafish at supraphysiological levels. One protein, insulin-like growth factor (Igf) binding-protein 1 (Igfbp1), potently promoted β-cell regeneration by potentiating α- to β-cell transdifferentiation...
September 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27503203/zebrafish-models-of-cardiovascular-disease
#13
Despina Bournele, Dimitris Beis
Cardiovascular disease (CVD) is one of the leading causes of death worldwide. The most significant risk factors associated with the development of heart diseases include genetic and environmental factors such as hypertension, high blood cholesterol levels, diabetes, smoking, and obesity. Coronary artery disease accounts for the highest percentage of CVD deaths and stroke, cardiomyopathies, congenital heart diseases, heart valve defects and arrhythmias follow. The causes, prevention, and treatment of all forms of cardiovascular disease remain active fields of biomedical research, with hundreds of scientific studies published on a weekly basis...
November 2016: Heart Failure Reviews
https://www.readbyqxmd.com/read/27425895/unconventional-neurotrophic-factors-cdnf-and-manf-structure-physiological-functions-and-therapeutic-potential
#14
Maria Lindahl, Mart Saarma, Päivi Lindholm
Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) promote the survival of midbrain dopaminergic neurons which degenerate in Parkinson's disease (PD). However, CDNF and MANF are structurally and functionally clearly distinct from the classical, target-derived neurotrophic factors (NTFs) that are solely secreted proteins. In cells, CDNF and MANF localize in the endoplasmic reticulum (ER) and evidence suggests that MANF, and possibly CDNF, is important for the maintenance of ER homeostasis...
July 14, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27406217/fucoxanthin-suppresses-lipid-accumulation-and-ros-production-during-differentiation-in-3t3-l1-adipocytes
#15
Min-Jung Seo, Young-Jin Seo, Cheol-Ho Pan, Ok-Hwan Lee, Kui-Jin Kim, Boo-Yong Lee
Fucoxanthin, a pigment from the chloroplasts of marine brown algae, has a number of effects against obesity, diabetes, inflammation and cancer and provides cerebrovascular protection. In this study, we investigated the inhibitory effects of fucoxanthin on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis. Treatment with fucoxanthin suppresses protein levels of the adipogenic transcription factors CCAAT/enhancer-binding protein alpha C/EBPα and peroxisome proliferator-activated receptor-γ and of their target protein, fatty acid binding protein 4...
July 13, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27341538/generation-of-parabiotic-zebrafish-embryos-by-surgical-fusion-of-developing-blastulae
#16
Elliott J Hagedorn, Jennifer L Cillis, Caitlyn R Curley, Taylor C Patch, Brian Li, Bradley W Blaser, Raquel Riquelme, Leonard I Zon, Dhvanit I Shah
Surgical parabiosis of two animals of different genetic backgrounds creates a unique scenario to study cell-intrinsic versus cell-extrinsic roles for candidate genes of interest, migratory behaviors of cells, and secreted signals in distinct genetic settings. Because parabiotic animals share a common circulation, any blood or blood-borne factor from one animal will be exchanged with its partner and vice versa. Thus, cells and molecular factors derived from one genetic background can be studied in the context of a second genetic background...
June 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27339277/impaired-constitutive-and-regenerative-neurogenesis-in-adult-hyperglycemic-zebrafish
#17
Anne-Claire Dorsemans, Stéphanie Soulé, Meltem Weger, Emmanuel Bourdon, Christian Lefebvre d'Hellencourt, Olivier Meilhac, Nicolas Diotel
A growing body of evidence supports hyperglycemia as a putative contributor to several brain dysfunctions observed in diabetes patients, such as impaired memory capacity, neural plasticity, and neurogenic processes. Thanks to the persistence of radial glial cells acting as neural stem cells, the brain of the adult zebrafish constitutes a relevant model to investigate constitutive and injury-induced neurogenesis in adult vertebrates. However, there is limited understanding of the impact of hyperglycemia on brain dysfunction in the zebrafish model...
June 23, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27312501/zebrafish-pancreas-as-a-model-for-development-and-disease
#18
R A Kimmel, D Meyer
The vertebrate pancreas is composed of acinar tissue that produces digestive enzymes, a ductal system for transporting those enzymes, and the endocrine islets which produce hormones critical for organism glucose homeostasis. Recent studies have highlighted similarities between zebrafish and mammals in organ development, and increasingly reveal that the regulation of metabolic homeostasis is highly conserved as well. Use of zebrafish as a model organism, with its ease of genetic manipulation, high fecundity, and ready access for imaging, has been highly productive for studies of islet cell development...
2016: Methods in Cell Biology
https://www.readbyqxmd.com/read/27263413/using-fluorescent-lipids-in-live-zebrafish-larvae-from-imaging-whole-animal-physiology-to-subcellular-lipid-trafficking
#19
J L Anderson, J D Carten, S A Farber
Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. Many aspects of how fatty acids and cholesterol are absorbed and processed by intestinal cells remain unclear and present a hurdle to developing approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism...
2016: Methods in Cell Biology
https://www.readbyqxmd.com/read/27148944/a-novel-small-molecule-ameliorates-ocular-neovascularisation-and-synergises-with-anti-vegf-therapy
#20
Rania S Sulaiman, Stephanie Merrigan, Judith Quigley, Xiaoping Qi, Bit Lee, Michael E Boulton, Breandán Kennedy, Seung-Yong Seo, Timothy W Corson
Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies...
2016: Scientific Reports
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