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https://www.readbyqxmd.com/read/27818940/critical-role-for-adenosine-receptor-a2a-in-%C3%AE-cell-proliferation
#1
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
#2
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...
October 31, 2016: 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
#3
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...
September 10, 2016: 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
#4
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
#5
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
#6
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
#7
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/27312501/zebrafish-pancreas-as-a-model-for-development-and-disease
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/26701651/serpinb1-promotes-pancreatic-%C3%AE-cell-proliferation
#12
Abdelfattah El Ouaamari, Ercument Dirice, Nicholas Gedeon, Jiang Hu, Jian-Ying Zhou, Jun Shirakawa, Lifei Hou, Jessica Goodman, Christos Karampelias, Guifeng Qiang, Jeremie Boucher, Rachael Martinez, Marina A Gritsenko, Dario F De Jesus, Sevim Kahraman, Shweta Bhatt, Richard D Smith, Hans-Dietmar Beer, Prapaporn Jungtrakoon, Yanping Gong, Allison B Goldfine, Chong Wee Liew, Alessandro Doria, Olov Andersson, Wei-Jun Qian, Eileen Remold-O'Donnell, Rohit N Kulkarni
Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates β cell proliferation in humans, mice, and zebrafish...
January 12, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/26658317/an-insulin-signaling-feedback-loop-regulates-pancreas-progenitor-cell-differentiation-during-islet-development-and-regeneration
#13
Lihua Ye, Morgan A Robertson, Teresa L Mastracci, Ryan M Anderson
As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation...
January 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/26393762/deviant-development-of-pancreatic-beta-cells-from-embryonic-exposure-to-pcb-126-in-zebrafish
#14
Alicia R Timme-Laragy, Karilyn E Sant, Michelle E Rousseau, Philip J diIorio
Exposures to co-planar PCBs and dioxins have been associated with diabetes in epidemiologic studies. Individuals may be predisposed to diseases such as diabetes as a result of exposure to environmental contaminants during early life, resulting in dysmorphic pancreatic islets or metabolically fragile β-cells. We tested the hypothesis that embryonic exposure to a model Ahr-ligand, PCB-126 would cause structural and/or functional alterations to the developing primary pancreatic islet in the zebrafish (Danio rerio)...
December 2015: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/26384018/diabetic-pdx1-mutant-zebrafish-show-conserved-responses-to-nutrient-overload-and-anti-glycemic-treatment
#15
Robin A Kimmel, Stefan Dobler, Nicole Schmitner, Tanja Walsen, Julia Freudenblum, Dirk Meyer
Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose. The hyperglycemia responds to pharmacologic anti-diabetic treatment and, as often seen in mammalian diabetes models, beta cells of pdx1 mutants show sensitivity to nutrient overload...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26364259/recovery-effect-of-phenylpropanoid-glycosides-from-magnolia-obovata-fruit-on-alloxan-induced-pancreatic-islet-damage-in-zebrafish-danio-rerio
#16
Kyeong-Hwa Seo, Youn-Hee Nam, Dae-Young Lee, Eun-Mi Ahn, Tong-Ho Kang, Nam-In Baek
Investigation of phytochemicals from Magnolia obovata fruit led to the isolation of three novel phenylpropanoid glycosides: obovatoside A-C (1-3) and two known phenylpropanoids, syringin (4) and pavonisol (5). The structures of 1-5 were determined by NMR, HRMS, IR and CD spectroscopic analyses. All compounds were evaluated for their effects on recovery from alloxan-induced pancreatic islet damage in zebrafish. All compounds increased the size of the injured pancreatic islet from 0.60- to 1.14-fold. Compounds 1 and 3-5 significantly increased glucose absorption in zebrafish...
October 30, 2015: Carbohydrate Research
https://www.readbyqxmd.com/read/26299433/polyamine-biosynthesis-is-critical-for-growth-and-differentiation-of-the-pancreas
#17
Teresa L Mastracci, Morgan A Robertson, Raghavendra G Mirmira, Ryan M Anderson
The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26211738/the-circular-rna-cdr1as-via-mir-7-and-its-targets-regulates-insulin-transcription-and-secretion-in-islet-cells
#18
Huanyu Xu, Sen Guo, Wei Li, Ping Yu
Among the identified thousands of circular RNAs (circRNA) in humans and animals, Cdr1as (also known as CiRS-7) was recently demonstrated to act as a powerful miR-7 sponge/inhibitor in developing midbrain of zebrafish, suggesting a novel mechanism for regulating microRNA functions. MiR-7 is abundantly expressed in islet cells, but overexpressing miR-7 in transgenic mouse β cells causes diabetes. Therefore, we infer that Cdr1as expression may inhibit miR-7 function in islet cells, which in turn improves insulin secretion...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26153247/centroacinar-cells-are-progenitors-that-contribute-to-endocrine-pancreas-regeneration
#19
Fabien Delaspre, Rebecca L Beer, Meritxell Rovira, Wei Huang, Guangliang Wang, Stephen Gee, Maria del Carmen Vitery, Sarah J Wheelan, Michael J Parsons
Diabetes is associated with a paucity of insulin-producing β-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in β-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch-responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors...
October 2015: Diabetes
https://www.readbyqxmd.com/read/26122662/nuclear-factor-%C3%AE%C2%BAb-inducing-kinase-activation-as-a-mechanism-of-pancreatic-%C3%AE-cell-failure-in-obesity
#20
Elisabeth K Malle, Nathan W Zammit, Stacey N Walters, Yen Chin Koay, Jianmin Wu, Bernice M Tan, Jeanette E Villanueva, Robert Brink, Tom Loudovaris, James Cantley, Shelli R McAlpine, Daniel Hesselson, Shane T Grey
The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo...
July 27, 2015: Journal of Experimental Medicine
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