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zebrafish diabetes

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https://www.readbyqxmd.com/read/29429148/fasiglifam-tak-875-a-g-protein-coupled-receptor-40-gpr40-agonist-may-induce-hepatotoxicity-through-reactive-oxygen-species-generation-in-a-gpr40-dependent-manner
#1
MinJeong Kim, Gyo Jeong Gu, Yun-Sook Koh, Su-Hyun Lee, Yi Rang Na, Seung Hyeok Seok, Kyung-Min Lim
Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration- (>50 μM) and time-dependent manners, both of which corresponded with ROS generation...
February 12, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29417450/zebrafish-as-a-model-for-toxicological-perturbation-of-yolk-and-nutrition-in-the-early-embryo
#2
REVIEW
Karilyn E Sant, Alicia R Timme-Laragy
PURPOSE OF REVIEW: Developmental toxicity assessments often focus on structural outcomes and overlook subtle metabolic differences which occur during the early embryonic period. Deviant embryonic nutrition can result in later-life disease, including diabetes, obesity, and cardiovascular disease. Prior to placenta-mediated nutrient exchange, the human embryo requires maternally supplied nutritional substrates for growth, called yolk. Here, we compare the biology of the human and zebrafish yolk and review examples of toxicant-mediated perturbation of yolk defects, composition, and utilization...
February 7, 2018: Current Environmental Health Reports
https://www.readbyqxmd.com/read/29364210/studying-diabetes-through-the-eyes-of-a-fish-microdissection-visualization-and-analysis-of-the-adult-tg-fli-egfp-zebrafish-retinal-vasculature
#3
Lucas Moritz Wiggenhauser, Katharina Kohl, Nadine Dietrich, Hans-Peter Hammes, Jens Kroll
Diabetic retinopathy is the leading cause of blindness among middle-aged adults. The rising prevalence of diabetes worldwide will make the prevention of diabetic microvascular complications one of the key research fields of the next decades. Specialized, targeted therapy and novel therapeutic drugs are needed to manage the increasing number of patients at risk of vision-loss. The zebrafish is an established animal model for developmental research questions with increasing relevance for modeling metabolic multifactorial disease processes...
December 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29351486/different-physiological-roles-of-insulin-receptors-in-mediating-nutrient-metabolism-in-zebrafish
#4
Bin-Yuan Yang, Gang Zhai, Yu-Long Gong, Jing-Zhi Su, Xu-Yan Peng, Guo-Hui Shang, Dong Han, Jun-Yan Jin, Hao-Kun Liu, Zhen-Yu Du, Zhan Yin, Shou-Qi Xie
Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a (insra) and b (insrb) caused β-cell hyperplasia and lethality from 5 dpf to 16 dpf. In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29306589/oxidative-stress-dependent-mmp-13-activity-underlies-glucose-neurotoxicity
#5
Ashley L Waldron, Patricia A Schroder, Kelly L Bourgon, Jessie K Bolduc, James L Miller, Adriana D Pellegrini, Amanda L Dubois, Magdalena Blaszkiewicz, Kristy L Townsend, Sandra Rieger
BACKGROUND: A complication of diabetes is neuropathy, a condition of sensory axon degeneration that originates in the epidermis. The mechanisms remain unknown but reactive oxygen species (ROS) have been implicated in this condition. In this study, we assessed the role of ROS and a candidate downstream target, MMP-13 in glucose-induced sensory axon degeneration in zebrafish and mice. METHODS: The effects of glucose on metabolism and sensory axon degeneration were assessed using qPCR and live imaging...
December 6, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29274062/metformin-beta-cell-development-and-novel-processes-following-beta-cell-ablation-in-zebrafish
#6
Georgia Wyett, Yann Gibert, Megan Ellis, Hozana A Castillo, Jan Kaslin, Kathryn Aston-Mourney
PURPOSE: Type 1 and 2 diabetes are characterized by a loss of insulin-producing beta-cells. Current treatments help maintain blood glucose levels but cannot provide a cure. As such, a vital target for the cure of diabetes is a way to restore beta-cell mass. The drug metformin can protect cultured beta-cells/islets from hyperglycemia-induced dysfunction and death. Further, treatment of pregnant mice with metformin results in an enhanced beta-cell fraction in the embryos; however, whether this occurs via a direct effect is unknown...
December 22, 2017: Endocrine
https://www.readbyqxmd.com/read/29242313/dissection-of-glomerular-transcriptional-profile-in-patients-with-diabetic-nephropathy-srgap2a-protects-podocyte-structure-and-function
#7
Yu Pan, Song Jiang, Qing Hou, Dandan Qiu, Jingsong Shi, Ling Wang, Zhaohong Chen, Mingchao Zhang, Aiping Duan, Weisong Qin, Ke Zen, Zhihong Liu
Podocytes play a pivotal role in maintaining glomerular filtration function through their interdigitated foot processes. However, the mechanisms that govern the podocyte cytoskeletal rearrangement still remain unclear. Through analyzing transcriptional profile of renal biopsy from diabetic nephropathy (DN) patients and control donors, we identify Slit-Robo GTP activating protein 2a (SRGAP2a) as one of the main 'hub' genes that are strongly associated with proteinuria and glomerular filtration in type 2 DN patients...
December 14, 2017: Diabetes
https://www.readbyqxmd.com/read/29234032/heat-failure-phenotypes-induced-by-knockdown-of-dapit-in-zebrafish-a-new-insight-into-mechanism-of-dilated-cardiomyopathy
#8
Yoji Nagata, Masakazu Yamagishi, Tetsuo Konno, Chiaki Nakanishi, Yoshihiro Asano, Shin Ito, Yuri Nakajima, Osamu Seguchi, Noboru Fujino, Masa-Aki Kawashiri, Seiji Takashima, Masafumi Kitakaze, Kenshi Hayashi
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetes-associated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. To determine whether USMG5 is related to the development of heart failure, we performed clinical and experimental studies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29217756/light-focusing-human-micro-lenses-derived-from-zebrafish-like-lens-cell-masses-model-lens-development-and-drug-induced-cataract-in-vitro
#9
Patricia Murphy, Md Humayun Kabir, Tarini Srivastava, Michele E Mason, Chitra Umala Dewi, Seakcheng Lim, Andrian Yang, Djordje Djordjevic, Murray C Killingsworth, Joshua W K Ho, David G Harman, Michael D O'Connor
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells...
December 7, 2017: Development
https://www.readbyqxmd.com/read/29203238/targeting-erythropoietin-protects-against-proteinuria-in-type-2-diabetic-patients-and-in-zebrafish
#10
Jianqing She, Zuyi Yuan, Yue Wu, Junfang Chen, Jens Kroll
OBJECTIVE: Adult human kidneys produce erythropoietin (EPO), which regulates red blood cell formation; however, whether EPO also functions directly on kidney development and controls diabetic kidney disease remains unknown. Here we analyzed the role of EPO in kidney development and under hyperglycemic conditions in zebrafish and in humans. METHODS: Diabetic patients and respective controls were enrolled in two cohorts. Serum EPO level and urine protein change upon human EPO administration were then analyzed...
November 22, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29165729/polyphenols-from-euphorbia-pekinensis-inhibit-ages-formation-in-vitro-and-vessel-dilation-in-larval-zebrafish-in-vivo
#11
Ik-Soo Lee, Seung-Hyun Jung, Jin Sook Kim
To identify active compounds in the roots of Euphorbia pekinensis for treatment of diabetic complications, an active column fraction from a 70% EtOH extract of E. pekinensis root was purified by preparative reversed-phase high-performance liquid chromatography, leading to the isolation of a new ellagic acid derivative, 3,3'-di-O-methylellagic acid 4-O-(6"-O-galloyl)-β-D-galactopyranoside (1), along with three known compounds, geraniin (2), 3,3'-di-O-methylellagic acid 4-O-β-D-xylopyranoside (3), and ellagic acid 3,3'-dimethyl ether (4)...
November 17, 2017: Planta Medica
https://www.readbyqxmd.com/read/29157806/trigonelline-promotes-auditory-function-through-nerve-growth-factor-signaling-on-diabetic-animal-models
#12
Rodrigo Castañeda, Isabel Rodriguez, Youn Hee Nam, Bin Na Hong, Tong Ho Kang
BACKGROUND: Protection of cochlear function and reconstruction of neuronal networks in damaged auditory sensory structures is crucial for therapeutic treatment of diabetic hearing loss. Nerve growth factor (NGF) has been used as a novel therapeutic target to protect against the neurodegenerative effects of Diabetes Mellitus (DM). PURPOSE: We aimed to evaluate the potential effect of trigonelline (TRG) on reducing auditory damage produced by DM using NGF as a potential marker...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29110609/bmp3-is-required-for-integrity-of-blood-brain-barrier-by-promoting-pericyte-coverage-in-zebrafish-embryos
#13
D Lei, X Jin, L Wen, H Dai, Z Ye, G Wang
BACKGROUND: The compromise of blood brain barrier (BBB) integrity is often associated with human hemorrhage stroke and neurodegeneration diseases, including retina diseases, such as age-related macular degeneration and diabetic retinopathy. Brain pericytes play pivotal roles in regulation and maintenance of BBB integrity. However, the mechanisms underlying brain pericyte development to establish BBB integrity remain unclear. METHODS: zebrafish transgenic lines Tg(flk1:GFP; gata1:dsRed), Tg(flk1:GFP), Tg(fli1:GFP) and Tg(BRE:GFP) were used in this work...
November 5, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29072584/impaired-sleep-circadian-rhythms-and-neurogenesis-in-diet-induced-premature-aging
#14
Alexander J Stankiewicz, Erin M McGowan, Lili Yu, Irina V Zhdanova
Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior...
October 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29057052/new-scaffold-for-angiogenesis-inhibitors-discovered-by-targeted-chemical-transformations-of-wondonin-natural-products
#15
Shuai Yu, Jedo Oh, Feng Li, Yongseok Kwon, Hyunkyung Cho, Jongheon Shin, Sang Kook Lee, Sanghee Kim
The structure of wondonin marine natural products was renovated to attain new drug-like scaffolds. Wondonins have novel antiangiogenic properties without overt cytotoxicity. However, the chemical instability and synthetic complexity of wondonins have hindered their development as a new type of antiangiogenesis agent. Using a structure-based bioisosterism, the benzodioxole moiety was changed to benzothiazole, and the imidazole moiety was replaced by 1,2,3-triazole. Our efforts resulted in a new scaffold with enhanced antiangiogenic activity and minimized cytotoxicity...
October 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29034193/comparative-study-of-herbal-plants-on-the-phenolic-and-flavonoid-content-antioxidant-activities-and-toxicity-on-cells-and-zebrafish-embryo
#16
Hassan Fahmi Ismail, Zanariah Hashim, Wong Tet Soon, Nur Syukriah Ab Rahman, Ain Nabihah Zainudin, Fadzilah Adibah Abdul Majid
Natural antioxidants derived from plants have shown a tremendous inhibitory effect on free radicals in actively metabolizing cells. Overproduction of free radicals increases the risk factor of chronic diseases associated with diabetes, cancer, arthritis and cardiovascular disease. Andrographis paniculata, Cinnamon zeylanicum, Curcuma xanthorrhiza, Eugenia polyantha and Orthosiphon stamineus are ethnomedicinal plants used in the Asian region to treat various illnesses from a common fever to metabolic disease...
October 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28986398/inhibition-of-cdk5-promotes-%C3%AE-cell-differentiation-from-ductal-progenitors
#17
Ka-Cheuk Liu, Gunter Leuckx, Daisuke Sakano, Philip A Seymour, Charlotte L Mattsson, Linn Rautio, Willem Staels, Yannick Verdonck, Palle Serup, Shoen Kume, Harry Heimberg, Olov Andersson
Inhibition of notch signalling is known to induce differentiation of endocrine cells in zebrafish and mouse. After performing an unbiased in vivo screen of ∼2200 small molecules in zebrafish we identified an inhibitor of Cdk5 (roscovitine), which potentiated formation of β-cells along the intra-pancreatic duct during concurrent inhibition of notch signalling. We confirmed and characterized the effect with a more selective Cdk5 inhibitor, (R)-DRF053, which specifically increased the number of duct-derived β-cells without affecting their proliferation...
October 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28946120/bisphenol-s-exposure-impairs-glucose-homeostasis-in-male-zebrafish-danio-rerio
#18
Fei Zhao, Guobin Jiang, Penghao Wei, Hongfang Wang, Shaoguo Ru
Bisphenol S (BPS) is a substitute of the plastic additive bisphenol A (BPA). Its concentrations detected in surface waters and urine samples are on the same order of magnitude as BPA. Human exposure to BPA has been implicated in the development of diabetes mellitus; however, whether BPS can disrupt glucose homeostasis and increase blood glucose concentration remains unclear. We extensively investigated the effects of environmentally relevant concentrations of BPS on glucose metabolism in male zebrafish (Danio rerio) and the underlying mechanisms of these effects...
January 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28925940/zebrafish-as-a-model-for-the-study-of-microvascular-complications-of-diabetes-and-their-mechanisms
#19
REVIEW
Karl Heckler, Jens Kroll
Diabetes mellitus (DM) is a crucial metabolic disease that leads to severe disorders. These include macrovascular complications such as myocardial infarction, stroke, and peripheral artery disease and microvascular complications including diabetic nephropathy, neuropathy, and retinopathy. Diabetes mellitus, along with its associated organ pathologies, is one of the key problems in today's medicine. Zebrafish is an upcoming disease model organism in diabetes research. Its glucose metabolism and the pathways of reactive metabolite formation are very similar to those of humans...
September 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28924380/intracellular-insulin-and-impaired-autophagy-in-a-zebrafish-model-and-a-cell-model-of-type-2-diabetes
#20
Xiang-Hui Meng, Bo Chen, Jing-Pu Zhang
Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin transcription level in liver, brain and muscle, and high fasting blood glucose in the high-fat diet zebrafish. Oppositely, the transcription levels of insulin substrate-2 and glucose transporter 2 were significantly decreased, indicating insulin signaling pathway and glucose transport impaired in the insulin-targeting tissues...
2017: International Journal of Biological Sciences
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