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https://www.readbyqxmd.com/read/28591638/interrupted-glucagon-signaling-reveals-hepatic-%C3%AE-cell-axis-and-role-for-l-glutamine-in-%C3%AE-cell-proliferation
#1
E Danielle Dean, Mingyu Li, Nripesh Prasad, Scott N Wisniewski, Alison Von Deylen, Jason Spaeth, Lisette Maddison, Anthony Botros, Leslie R Sedgeman, Nadejda Bozadjieva, Olga Ilkayeva, Anastasia Coldren, Greg Poffenberger, Alena Shostak, Michael C Semich, Kristie I Aamodt, Neil Phillips, Hai Yan, Ernesto Bernal-Mizrachi, Jackie D Corbin, Kasey C Vickers, Shawn E Levy, Chunhua Dai, Christopher Newgard, Wei Gu, Roland Stein, Wenbiao Chen, Alvin C Powers
Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However, interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation, we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse, zebrafish, and human α cells was mTOR and FoxP transcription factor dependent. Changes in hepatic amino acid (AA) catabolism gene expression predicted the observed increase in circulating AAs...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28393070/assessment-of-toxicological-perturbations-and-variants-of-pancreatic-islet-development-in-the-zebrafish-model
#2
Karilyn E Sant, Haydee M Jacobs, Jiali Xu, Katrina A Borofski, Larry G Moss, Jennifer B Moss, Alicia R Timme-Laragy
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio)...
September 2016: Toxics
https://www.readbyqxmd.com/read/28386438/expression-and-function-of-atp-dependent-potassium-channels-in-zebrafish-islet-%C3%AE-cells
#3
Christopher H Emfinger, Alecia Welscher, Zihan Yan, Yixi Wang, Hannah Conway, Jennifer B Moss, Larry G Moss, Maria S Remedi, Colin G Nichols
ATP-sensitive potassium channels (KATP channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, KATP channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism-secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear. In this paper, we demonstrate that zebrafish islet β-cells express functional KATP channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts...
February 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28347780/semaphorin4d-promotes-axon-regrowth-and-swimming-ability-during-recovery-following-zebrafish-spinal-cord-injury
#4
Shi-Xiao Peng, Li Yao, Chun Cui, Hou-de Zhao, Chun-Jie Liu, Yu-Hong Li, Lin-Fang Wang, Shu-Bing Huang, Yan-Qin Shen
Semaphorins comprise a family of proteins involved in axon guidance during development. Semaphorin4D (Sema4D) has both neuroregenerative and neurorepressive functions, being able to stimulate both axonal outgrowth and growth cone collapse during development, and therefore could play an important role in neurological recovery from traumatic injury. Here, we used a zebrafish spinal cord transection model to study the role of Sema4D in a system capable of neuroregeneration. Real-time qPCR and in situ hybridization showed upregulated Sema4D expression in the acute response phase (within 3days post SCI), and downregulated levels in the chronic response phase (11-21days after SCI)...
March 25, 2017: Neuroscience
https://www.readbyqxmd.com/read/28335861/zebrafish-pancreas-development-and-regeneration-fishing-for-diabetes-therapies
#5
REVIEW
Victoria E Prince, Ryan M Anderson, Gokhan Dalgin
The zebrafish pancreas shares its basic organization and cell types with the mammalian pancreas. In addition, the developmental pathways that lead to the establishment of the pancreatic islets of Langherhans are generally conserved from fish to mammals. Zebrafish provides a powerful tool to probe the mechanisms controlling establishment of the pancreatic endocrine cell types from early embryonic progenitor cells, as well as the regeneration of endocrine cells after damage. This knowledge is, in turn, applicable to refining protocols to generate renewable sources of human pancreatic islet cells that are critical for regulation of blood sugar levels...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28129847/analysis-of-pancreatic-disease-in-zebrafish
#6
S C Eames Nalle, K F Franse, M D Kinkel
One of the appeals of the zebrafish model is the relative ease of studying disease progression from embryonic or larval stages through to adulthood. Because of this, the zebrafish has become an important model for postembryonic pancreatic disease, particularly diabetes and pancreatic cancer. Here we present methods for using the adult zebrafish to analyze pancreas function and structure, with an emphasis on the endocrine pancreas and the beta cells. The methods include fasting, weighing adults, and anesthetizing adults, and intraperitoneal injection of glucose based on body weight...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28123328/enhanced-antidiabetic-efficacy-and-safety-of-compound-k%C3%A2-%C3%AE-cyclodextrin-inclusion-complex-in-zebrafish
#7
Youn Hee Nam, Hoa Thi Le, Isabel Rodriguez, Eun Young Kim, Keonwoo Kim, Seo Yule Jeong, Sang Ho Woo, Yeong Ro Lee, Rodrigo Castañeda, Jineui Hong, Min Gun Ji, Ung-Jin Kim, Bin Na Hong, Tae Woo Kim, Tong Ho Kang
BACKGROUND: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic β-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. METHODS: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with β-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model...
January 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28106108/isl2b-regulates-anterior-second-heart-field-development-in-zebrafish
#8
Hagen R Witzel, Sirisha Cheedipudi, Rui Gao, Didier Y R Stainier, Gergana D Dobreva
After initial formation, the heart tube grows by addition of second heart field progenitor cells to its poles. The transcription factor Isl1 is expressed in the entire second heart field in mouse, and Isl1-deficient mouse embryos show defects in arterial and venous pole development. The expression of Isl1 is conserved in zebrafish cardiac progenitors; however, Isl1 is required for cardiomyocyte differentiation only at the venous pole. Here we show that Isl1 homologues are expressed in specific patterns in the developing zebrafish heart and play distinct roles during cardiac morphogenesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27916275/artemisinins-target-gabaa-receptor-signaling-and-impair-%C3%AE-cell-identity
#9
COMMENT
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...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/27818940/critical-role-for-adenosine-receptor-a2a-in-%C3%AE-cell-proliferation
#10
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
#11
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/27614453/the-circular-rna-cirs-7-cdr1as-acts-as-a-risk-factor-of-hepatic-microvascular-invasion-in-hepatocellular-carcinoma
#12
Liangliang Xu, Ming Zhang, Xiaobo Zheng, Pengsheng Yi, Chuan Lan, Mingqing Xu
PURPOSE: Circular RNAs (circRNA) represent a novel class of widespread and diverse endogenous RNAs that regulate gene expression in mammals. microRNA-7 (miR-7) is a well-demonstrated suppressor of hepatocellular carcinoma (HCC). Recent studies have showed that one such circRNA, ciRS-7 (also termed as Cdr1as) was the inhibitor and sponge of miR-7 in the embryonic zebrafish midbrain and islet cells. However, the relationships among ciRS-7, miR-7 and clinical features of HCC remain to be clarified...
January 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27565026/sox9b-is-a-mediator-of-retinoic-acid-signaling-restricting-endocrine-progenitor-differentiation
#13
Wei Huang, Rebecca L Beer, Fabien Delaspre, Guangliang Wang, Hannah E Edelman, Hyewon Park, Mizuki Azuma, Michael J Parsons
Centroacinar cells (CACs) are ductal Notch-responsive progenitors that in the larval zebrafish pancreas differentiate to form new islets and ultimately contribute to the majority of the adult endocrine mass. Uncovering the mechanisms regulating CAC differentiation will facilitate understanding how insulin-producing β cells are formed. Previously we reported retinoic acid (RA) signaling and Notch signaling both regulate larval CAC differentiation, suggesting a shared downstream intermediate. Sox9b is a transcription factor important for islet formation whose expression is upregulated by Notch signaling in larval CACs...
October 1, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27516442/igfbp1-increases-%C3%AE-cell-regeneration-by-promoting-%C3%AE-to-%C3%AE-cell-transdifferentiation
#14
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/27488665/insulin-and-sgk1-reduce-the-function-of-na-monocarboxylate-transporter-1-smct1-slc5a8
#15
Adriana López-Barradas, Tania González-Cid, Norma Vázquez, Marisol Gavi-Maza, Adriana Reyes-Camacho, Laura A Velázquez-Villegas, Victoria Ramírez, Kambiz Zandi-Nejad, David B Mount, Nimbe Torres, Armando R Tovar, Michael F Romero, Gerardo Gamba, Consuelo Plata
SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition of insulin reduced α-keto-isocaproate (KIC)-dependent (22)Na(+) uptake by 29%. Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased the KIC-dependent (22)Na(+) uptake by 34%...
November 1, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27425895/unconventional-neurotrophic-factors-cdnf-and-manf-structure-physiological-functions-and-therapeutic-potential
#16
REVIEW
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...
January 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27312501/zebrafish-pancreas-as-a-model-for-development-and-disease
#17
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/27285162/large-scale-scanning-transmission-electron-microscopy-nanotomy-of-healthy-and-injured-zebrafish-brain
#18
Jeroen Kuipers, Ruby D Kalicharan, Anouk H G Wolters, Tjakko J van Ham, Ben N G Giepmans
Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae(1-7). Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27110541/human-bone-marrow-subpopulations-sustain-human-islet-function-and-viability-in-vitro
#19
Lu Guang Luo, Fang Xiong, Philippe Ravassard, John Zq Luo
AIMS: Allogeneic bone marrow (BM) has been shown to support human islet survival and function in long-term culture by initiating human islet vascularization and β-cell regeneration. Various BM subpopulations may play different roles in human islet functions and survival. In this paper we investigated the effects of BM and its subpopulations, endothelial progenitor cells (E) and mesenchymal (M) cells on human islet's β-cell function and regeneration. STUDY DESIGN: Isolation and identification of subpopulations from human bone marrow and culture with allogeneic human islet to investigate effects of different cell population on human islet function and regeneration...
2015: British Journal of Medicine and Medical Research
https://www.readbyqxmd.com/read/26757817/transcription-factors-and-dna-repair-enzymes-compete-for-damaged-promoter-sites
#20
Stephen P G Moore, Joshua Kruchten, Kimberly J Toomire, Phyllis R Strauss
Transcriptional regulation is a tightly regulated, vital process. The transcription factor cyclic AMP-response element-binding protein 1 (CREB1) controls ∼25% of the mammalian transcriptome by binding the CREB1 binding site consensus sequence (CRE) sequence (TGACGTCA). DNA lesions within CRE modulate CREB1 binding negatively and positively. Because appropriate DNA lesions also interact with base excision repair proteins, we investigated whether CREB1 and repair glycosylases compete with each other. We incubated 39-mer CRE-containing double-stranded oligonucleotides with recombinant CREB1 alone or with UNG2 or OGG1, followed by EMSA...
March 11, 2016: Journal of Biological Chemistry
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