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https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#1
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28228865/identification-of-beta-cell-dysfunction-at-the-pre-symptomatic-stage-of-diabetes-mellitus-by-novel-analytical-system-liquid-biopsy-measurements-in-femtograms
#2
REVIEW
Kurt Krapfenbauer
BACKGROUND: Diabetes mellitus is produced and progresses as a consequence of complex and gradual processes, in which a variety of alterations of the endocrine pancreas, are involved and which mainly result in beta cell failure. Those molecular alterations can be found in the bloodstream, which suggests that we could quantify specific biomarkers in plasma or serum by very sensitive methods before the onset diabetes mellitus is diagnosed. However, classical methods of protein analysis such as electrophoresis, Western blot, ELISA, and liquid chromatography are generally time-consuming, lab-intensive, and not sensitive enough to detect such alteration in a pre-symptomatic state of the disease...
December 2017: EPMA Journal
https://www.readbyqxmd.com/read/28167928/clinical-review-of-antidiabetic-drugs-implications-for-type-2-diabetes-mellitus-management
#3
REVIEW
Arun Chaudhury, Chitharanjan Duvoor, Vijaya Sena Reddy Dendi, Shashank Kraleti, Aditya Chada, Rahul Ravilla, Asween Marco, Nawal Singh Shekhawat, Maria Theresa Montales, Kevin Kuriakose, Appalanaidu Sasapu, Alexandria Beebe, Naveen Patil, Chaitanya K Musham, Govinda Prasad Lohani, Wasique Mirza
Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28152182/reprogramming-of-pancreatic-acinar-cells-to-functional-beta-cells-by-in-vivo-transduction-of-a-polycistronic-construct-containing-pdx1-ngn3-mafa-in-mice
#4
C Cavelti-Weder, A Zumsteg, W Li, Q Zhou
To generate new beta cells after birth is a key focus of regenerative medicine, which could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: (1) the development of beta cells from putative precursor cells of the adult pancreas, which is termed neogenesis, (2) replication of existing beta cells, (3) differentiation from embryonic or induced pluripotent stem cells, and (4) reprogramming of non-beta cells to beta cells. Studies from the authors' laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA...
February 2, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28149833/assessment-of-the-link-between-in-utero-exposure-to-2-aminoanthracene-2aa-and-type-1-diabetes-t1d
#5
Christopher A Mays, Daniel A Hunter, Wilson Yau, Worlanyo E Gato
BACKGROUND: A recent diabetes report revealed an increased incidence in diabetes including type 1-diabetes (T1D). The increase in the numbers of T1D incidences are thought to be related to environmental reasons such as the exposure to environmental chemicals including arylamine 2-aminoanthracene (2AA). T1D is an autoimmune disease of the pancreatic islet in which insulin-producing beta cells are destroyed by auto-reactive T-cells and monocytic cells. METHODS: The purpose of this study is to examine the extent to which 2AA exposure contributes to T1D...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28149012/filarial-abundant-larval-transcript-protein-alt-2-an-immunomodulatory-therapeutic-agent-for-type-1-diabetes
#6
Sridhar M Reddy, Pooja M Reddy, Nitin Amdare, Vishal Khatri, Aaditya Tarnekar, Kalyan Goswami, Maryada Venkata Rami Reddy
Type 1 diabetes (T1D) that accounts for about 5-10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasite Brugia malayi (rBmALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28146100/echovirus-6-infects-human-exocrine-and-endocrine-pancreatic-cells-and-induces-pro-inflammatory-innate-immune-response
#7
Luis Sarmiento, Gun Frisk, Mahesh Anagandula, Monika Hodik, Ilaria Barchetta, Eitan Netanyah, Eduardo Cabrera-Rode, Corrado M Cilio
Human enteroviruses (HEV), especially coxsackievirus serotype B (CVB) and echovirus (E), have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types...
January 30, 2017: Viruses
https://www.readbyqxmd.com/read/28144955/hypothyroidism-in-utero-stimulates-pancreatic-beta-cell-proliferation-and-hyperinsulinaemia-in-the-ovine-fetus-during-late-gestation
#8
Shelley E Harris, Miles J De Blasio, Melissa A Davis, Amy C Kelly, Hailey M Davenport, F B Peter Wooding, Dominique Blache, David Meredith, Miranda Anderson, Abigail L Fowden, Sean W Limesand, Alison J Forhead
Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero...
January 31, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28137793/increase-in-pancreatic-proinsulin-and-preservation-of-beta-cell-mass-in-autoantibody-positive-donors-prior-to-type-1-diabetes-onset
#9
Teresa Rodriguez-Calvo, Jose Zapardiel-Gonzalo, Natalie Amirian, Ericka Castillo, Yasaman Lajevardi, Lars Krogvold, Knut Dahl-Jørgensen, Matthias G von Herrath
Type 1 diabetes is characterized by the loss of insulin production due to beta cell dysfunction and/or destruction. The hypothesis that beta cell loss occurs early during the pre-diabetic phase has recently been challenged. Here we show, for the first time in situ that in pancreas sections from autoantibody positive donors (Ab+) insulin area and beta cell mass are maintained prior to disease onset, and that production of proinsulin increases. This suggests that beta cell destruction occurs more precipitously than previously assumed...
January 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28129847/analysis-of-pancreatic-disease-in-zebrafish
#10
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/28114938/closed-loop-for-type-1-diabetes-an-introduction-and-appraisal-for-the-generalist
#11
EDITORIAL
Lia Bally, Hood Thabit, Roman Hovorka
BACKGROUND: Rapid progress over the past decade has been made with the development of the 'Artificial Pancreas', also known as the closed-loop system, which emulates the feedback glucose-responsive functionality of the pancreatic beta cell. The recent FDA approval of the first hybrid closed-loop system makes the Artificial Pancreas a realistic therapeutic option for people with type 1 diabetes. In anticipation of its advent into clinical care, we provide a primer and appraisal of this novel therapeutic approach in type 1 diabetes for healthcare professionals and non-specialists in the field...
January 23, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#12
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28067253/whole-organ-and-islet-of-langerhans-dosimetry-for-calculation-of-absorbed-doses-resulting-from-imaging-with-radiolabeled-exendin
#13
Inge van der Kroon, Wietske Woliner-van der Weg, Maarten Brom, Lieke Joosten, Cathelijne Frielink, Mark W Konijnenberg, Eric P Visser, Martin Gotthardt
Radiolabeled exendin is used for non-invasive quantification of beta cells in the islets of Langerhans in vivo. High accumulation of radiolabeled exendin in the islets raised concerns about possible radiation-induced damage to these islets in man. In this work, islet absorbed doses resulting from exendin-imaging were calculated by combining whole organ dosimetry with small scale dosimetry for the islets. Our model contains the tissues with high accumulation of radiolabeled exendin: kidneys, pancreas and islets...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039581/microrna-expression-profiles-of-human-ipscs-differentiation-into-insulin-producing-cells
#14
Guido Sebastiani, Marco Valentini, Giuseppina Emanuela Grieco, Giuliana Ventriglia, Laura Nigi, Francesca Mancarella, Silvia Pellegrini, Gianvito Martino, Valeria Sordi, Lorenzo Piemonti, Francesco Dotta
AIMS: MicroRNAs are a class of small noncoding RNAs, which control gene expression by inhibition of mRNA translation. MicroRNAs are involved in the control of biological processes including cell differentiation. Here, we aim at characterizing microRNA expression profiles during differentiation of human induced pluripotent stem cells (hiPSCs) into insulin-producing cells. METHODS: We differentiated hiPSCs toward endocrine pancreatic lineage following a 18-day protocol...
December 30, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/28032446/magnetic-resonance-imaging-of-intra-pancreatic-ductal-nanoparticle-delivery-to-islet-cells
#15
Ping Wang, Alana Ross, Byunghee Yoo, Jingsheng Yang, Christian Farrar, Chongzhao Ran, Pamela Pantazopoulos, Zdravka Medarova, Anna Moore
The absence of reliable drug delivery systems to pancreatic beta-cells hampers efficient treatment of type 1 diabetes. Nanoparticle delivery systems equipped with imaging capabilities could enable selective delivery to pancreatic islet cells. Biodistribution of nanoparticles is defined by several factors including the mode of administration, which determines accumulation in various organs. In this study we tested whether intra-pancreatic ductal injection of magnetic nanoparticles (MN) would result in efficient cellular uptake by pancreatic islet cells...
December 29, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28028829/localization-of-nucleic-acid-sensing-toll-like-receptors-in-human-and-mouse-pancreas
#16
Olli Helminen, Heikki Huhta, Joonas H Kauppila, Petri P Lehenkari, Juha Saarnio, Tuomo J Karttunen
Nucleic acid-sensing toll-like receptors (TLRs) (3, 7, 8, 9) have a role both in antiviral innate immunity and in autoimmune disorders. We assessed the expression of TLR3, 7, 8 and 9 in human and mouse pancreas focusing on the subpopulations of cells in the Langerhans islets. We studied eight human samples with normal pancreatic islets and two samples from patients with type 1 diabetes. Additionally, 10 CD-1 mouse pancreases were analysed. Immunohistochemical double-stainings for the TLRs and insulin, glucagon or somatostatin, respectively, were performed along with appropriate controls...
February 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28024793/recombinant-interferon-alpha-2b-is-a-high-affinity-antigen-for-type-1-diabetes-autoantibodies
#17
Wahid Ali Khan
OBJECTIVES: Type 1 diabetes results from T-cell-mediated destruction of the beta cells of the pancreas and is associated with several autoimmune phenomena. Many studies have suggested the involvement of interferon alpha (IFN α) in the development of type 1 diabetes, but the exact mechanism remains unclear. In this study, the binding of type 1 diabetes antibodies with recombinant interferon alpha-2b (hrIFN α-2b), their gene (cIFN α-2b gene) and commercially available interferon α-2b (IFN α-2b) were assessed...
December 23, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28017702/arsenite-in-drinking-water-produces-glucose-intolerance-in-pregnant-rats-and-their-female-offspring
#18
María Marta Bonaventura, Nadia Soledad Bourguignon, Marianne Bizzozzero, Diego Rodriguez, Clara Ventura, Claudia Cocca, Carlos Libertun, Victoria Adela Lux-Lantos
Drinking water is the main source of arsenic exposure. Chronic exposure has been associated with metabolic disorders. Here we studied the effects of arsenic on glucose metabolism, in pregnant and post-partum of dams and their offspring. We administered 5 (A5) or 50 (A50) mg/L of sodium arsenite in drinking water to rats from gestational day 1 (GD1) until two months postpartum (2MPP), and to their offspring from weaning until 8 weeks old. Liver arsenic dose-dependently increased in arsenite-treated rats to levels similar to exposed population...
February 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28012279/pancreas-volume-and-fat-deposition-in-diabetes-and-normal-physiology-consideration-of-the-interplay-between-endocrine-and-exocrine-pancreas
#19
Yoshifumi Saisho
The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes...
July 2016: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#20
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
February 2017: Biochimie
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