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Pancreas beta cells

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https://www.readbyqxmd.com/read/28924486/expression-of-transcription-factors-in-men1-associated-pancreatic-neuroendocrine-tumors
#1
Yasutaka Takeda, Yukihiro Fujita, Kentaro Sakai, Tomoe Abe, Tomonobu Nakamura, Tsuyoshi Yanagimachi, Hidemitsu Sakagami, Jun Honjo, Atsuko Abiko, Yuichi Makino, Masakazu Haneda
MEN1-associated pancreatic neuroendocrine tumors (pNETs) may potentially express distinct hormones, but the mechanism has not been elucidated. Transcription factors such as MafA and Pdx1 have been identified to lead to beta cell differentiation, while Arx and Brn4 to alpha cell differentiation in developing pancreas. We hypothesized those transcription factors are important to produce specific hormones in pNETs, similarly to developing pancreas, and examined the expression of transcription factors in a case of MEN1 who showed immunohistological coexistence of several hormone-producing pNETs including insulinoma...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28921917/changes-on-the-pancreas-in-experimental-diabetes-and-the-effect-of-lycopene-on-these-changes-pdx-1-ngn-3-and-nestin-expressions
#2
Mustafa Sandıkcı, Levent Karagenc, Mustafa Yıldız
The aim of the present study was to investigate changes occurring in the number of beta cells, as well as the expressions of Ngn-3, nestin and Pdx-1 of pancreatic progenitor cells in the pancreas of experimentally-induced adult diabetic rats and to determine the effect of orally-administered lycopene on these changes. Following the administration of 50 mg/kg streptozotocin to rats, four groups of animals were established: control+corn oil, control+lycopene, diabetic+corn oil and diabetic+lycopene. The animals in the control+lycopene and diabetic+lycopene groups received 4 mg/kg lycopene for a period of four weeks...
September 16, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28892926/antidiabetic-activity-of-aqueous-extract-of-solanum-nigrum-linn-berries-in-alloxan-induced-diabetic-wistar-albino-rats
#3
M S Umamageswari, T M Karthikeyan, Yasmeen A Maniyar
INTRODUCTION: Solanum nigrum Linn. is a common medicinal plant possessing a wide variety of pharmacological activity. Current treatment of diabetes mellitus has plenty of adverse effects necessitating the search of alternate drugs. AIM: Evaluation of antidiabetic effect of Aqueous Extract of Solanum Nigrum Linn Berries (AESNB) in alloxan induced diabetic Wistar rats. MATERIALS AND METHODS: There were five groups (normal control, diabetic control, AESNB 200 mg/kg/day, ASENB 400 mg/kg/day and standard i...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891030/species-differences-in-pancreatic-binding-of-do3a-vs-cys-40-exendin4
#4
Olof Eriksson, Ulrika Rosenström, Ram K Selvaraju, Barbro Eriksson, Irina Velikyan
AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed. METHODS: In vitro and ex vivo autoradiography studies of pancreas were performed using [(177)Lu]Lu-DO3A-VS-Cys(40)-Exendin4, in order to investigate the mechanism of uptake as well as the islet uptake contrast in mouse, rat, pig, and non-human primate...
September 11, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28884202/gcg-creert2-knockin-mice-as-a-tool-for-genetic-manipulation-in-pancreatic-alpha-cells
#5
Chiyo Shiota, Krishna Prasadan, Ping Guo, Joseph Fusco, Xiangwei Xiao, George K Gittes
AIMS/HYPOTHESIS: The Cre/loxP system, which enables tissue-specific manipulation of genes, is widely used in mice for diabetes research. Our aim was to develop a new Cre-driver mouse line for the specific and efficient manipulation of genes in pancreatic alpha cells. METHODS: A Gcg (CreERT2) knockin mouse, which expresses a tamoxifen-inducible form of Cre from the endogenous preproglucagon (Gcg) gene locus, was generated by homologous recombination. The new Gcg (CreERT2) mouse line was crossed to the Rosa26 (tdTomato) (R26 (tdTomato) ) Cre reporter mouse line in order to evaluate the tissue specificity, efficiency and tamoxifen dependency of Gcg (CreERT2) -mediated recombination...
September 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28877912/type-1-interferons-potentiate-human-cd8-t-cell-cytotoxicity-through-a-stat4-and-granzyme-b-dependent-pathway
#6
Brittney N Newby, Todd M Brusko, Baiming Zou, Mark A Atkinson, Michael Clare-Salzler, Clayton E Mathews
Events defining the progression to human type 1 diabetes (T1D) have remained elusive owing to the complex interaction between genetics, the immune system, and the environment. Type 1 Interferons (T1-IFN) are known to be a constituent of the auto-inflammatory milieu within the pancreas of patients with T1D. However, the capacity of IFNα/β to modulate human activated auto-reactive CD8(+) T cell (CTL) responses within the islets of patients with T1D have not been investigated. Here, we engineer human beta cell specific CTLs and demonstrate that T1-IFN augments cytotoxicity by inducing rapid phosphorylation of STAT4, resulting in direct binding at the granzyme B (GZMB) promoter within 2 hours of exposure...
September 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28877242/comparative-quantitative-proteomic-analysis-of-disease-stratified-laser-captured-microdissected-human-islets-identifies-proteins-and-pathways-potentially-related-to-type-1-diabetes
#7
Julius O Nyalwidhe, Wojciech J Grzesik, Tanya C Burch, Michele L Semeraro, Tayab Waseem, Ivan C Gerling, Raghavendra G Mirmira, Margaret A Morris, Jerry L Nadler
Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. The goal of this study was to identify novel protein signatures that distinguish Islets from patients with T1D, patients who are autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated autoantibodies in the absence of diabetes, and donors with T1D...
2017: PloS One
https://www.readbyqxmd.com/read/28832685/oxygen-environment-and-islet-size-are-the-primary-limiting-factors-of-isolated-pancreatic-islet-survival
#8
Hirotake Komatsu, Colin Cook, Chia-Hao Wang, Leonard Medrano, Henry Lin, Fouad Kandeel, Yu-Chong Tai, Yoko Mullen
BACKGROUND: Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency. METHODOLOGY: The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model...
2017: PloS One
https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#9
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28819632/detection-of-islet-cell-immune-reactivity-with-low-glycemic-index-foods-is-this-a-concern-for-type-1-diabetes
#10
Datis Kharrazian, Martha Herbert, Aristo Vojdani
Dietary management of autoimmune diabetes includes low glycemic foods classified from the glycemic index, but it does not consider the role that immunoreactive foods may play with the immunological etiology of the disease. We measured the reactivity of either monoclonal or polyclonal affinity-purified antibodies to insulin, insulin receptor alpha, insulin receptor beta, zinc transporter 8 (ZnT8), tyrosine phosphatase-based islet antigen 2 (IA2), and glutamic acid decarboxylase (GAD) 65 and 67 against 204 dietary proteins that are commonly consumed...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28812213/heterogeneity-in-the-beta-cell-population-a-guided-search-into-its-significance-in-pancreas-and-in-implants
#11
REVIEW
Daniel Pipeleers, Ines De Mesmaeker, Thomas Robert, Freya Van Hulle
PURPOSE OF REVIEW: Intercellular differences in function have since long been noticed in the pancreatic beta-cell population. Heterogeneity in cellular glucose responsiveness is considered of physiological and pathological relevance. The present review updates evidence for the physiologic significance of beta-cell heterogeneity in the pancreas. It also briefly discusses what this role would imply for beta-cell implants in diabetes. RECENT FINDINGS: Over the past 3 years, functionally different beta cells have been related to mechanisms that may underlie their heterogeneity in the pancreas, such as the stage in their life cycle and the degree of their clustering to islets with varying vascularization...
August 15, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28793277/o-2-18-f-fluoroethyl-l-tyrosine-18-f-fet-uptake-in-insulinoma-first-results-from-a-xenograft-mouse-model-and-from-human
#12
Alessio Imperiale, Frédéric Boisson, Guillaume Kreutter, Bernard Goichot, Izzie Jacques Namer, Philippe Bachellier, Patrice Laquerriere, Laurence Kessler, Patrice Marchand, David Brasse
INTRODUCTION: Herein we have evaluated the uptake of O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) in insulinoma in comparison with those of 6-(18)F-fluoro-3,4-dihydroxy-l-phenylalanine ((18)F-FDOPA) providing first data from both murine xenograft model and one patient with proved endogenous hyperinsulinemic hypoglycemia. METHODS: Dynamic (18)F-FET and carbidopa-assisted (18)F-FDOPA PET were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F murine beta cells and on a 30-year-old man with type-1 multiple endocrine neoplasia and hyperinsulinemic hypoglycemia defined by a positive fasting test...
July 12, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28791439/metabolic-crosstalk-between-fatty-pancreas-and-fatty-liver-effects-on-local-inflammation-and-insulin-secretion
#13
Felicia Gerst, Robert Wagner, Gabriele Kaiser, Madhura Panse, Martin Heni, Jürgen Machann, Malte N Bongers, Tina Sartorius, Bence Sipos, Falko Fend, Christian Thiel, Silvio Nadalin, Alfred Königsrainer, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Susanne Ullrich, Dorothea Siegel-Axel
AIMS/HYPOTHESIS: Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. METHODS: Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68...
August 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28789815/bioprinting-and-cellular-therapies-for-type-1-diabetes
#14
REVIEW
Dino J Ravnic, Ashley N Leberfinger, Ibrahim T Ozbolat
Type 1 diabetes mellitus is a chronic autoimmune disease that results from the destruction of beta (β) cells in the pancreatic islets, leading to loss of insulin production and resultant hyperglycemia. Recent developments in stem cell biology have generated much excitement for β-cell replacement strategies; β cells are one of many cell types in the complex islet environment and pancreas. In this Opinion, we discuss recent successful attempts to generate β cells and how this can be coupled with bioprinting technologies in order to fabricate pancreas tissues, which holds great potential for type 1 diabetes...
August 5, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28770422/depletion-of-beta-cell-intranuclear-rodlets-in-human-type-ii-diabetes
#15
Yi Yuan Zhou, Soufiane El Hallani, Fady Balaa, Waleed Mohammad, Douglas A Gray, John Woulfe
Intranuclear rodlets (INRs) are rod-shaped intranuclear bodies of unknown function present in the nuclei of pancreatic beta cells. Previous studies have demonstrated a significant depletion of INRs from beta cells in mouse models of type II diabetes, suggesting that they may have pathological significance. The objective of the present study was to determine whether beta cell INRs show quantitative alterations in human type II diabetes. In sections of non-neoplastic pancreas from 23 diabetic patients and 23 controls who had undergone complete or partial pancreatectomy, we detected a significant reduction in the proportion of INRs in insulin-immunoreactive beta cells...
August 2, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28770318/regulatory-t-cell-dysfunction-in-type-1-diabetes-what-s-broken-and-how-can-we-fix-it
#16
REVIEW
Caroline M Hull, Mark Peakman, Timothy I M Tree
Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4(+) and CD8(+) T cells with specificity for islet autoantigens...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28761107/regulatory-t-cells-from-pancreatic-lymphnodes-of-patients-with-type-1-diabetes-express-increased-levels-of-microrna-mir-125a-5p-that-limits-ccr2-expression
#17
Guido Sebastiani, Giuliana Ventriglia, Angela Stabilini, Carlo Socci, Cristina Morsiani, Andrea Laurenzi, Laura Nigi, Caterina Formichi, Bechara Mfarrej, Alessandra Petrelli, Georgia Fousteri, Todd M Brusko, Francesco Dotta, Manuela Battaglia
Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754350/beneficial-metabolic-effects-of-dietary-epigallocatechin-gallate-alone-and-in-combination-with-exendin-4-in-high-fat-diabetic-mice
#18
Nupur M Pathak, Paul J B Millar, Varun Pathak, Peter R Flatt, Victor A Gault
OBJECTIVE: Significant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. METHODS: EGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin...
July 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28753672/an-increase-in-immature-%C3%AE-cells-lacking-glut2-precedes-the-expansion-of-%C3%AE-cell-mass-in-the-pregnant-mouse
#19
Christine A Beamish, Linhao Zhang, Sandra K Szlapinski, Brenda J Strutt, David J Hill
A compensatory increase in β-cell mass occurs during pregnancy to counter the associated insulin resistance, and a failure in adaptation is thought to contribute to gestational diabetes. Insulin-expressing but glucose-transporter-2-low (Ins+Glut2LO) progenitor cells are present in mouse and human pancreas, being predominantly located in extra-islet β-cell clusters, and contribute to the regeneration of the endocrine pancreas following induced ablation. We therefore sought to investigate the contribution of Ins+Glut2LO cells to β-cell mass expansion during pregnancy...
2017: PloS One
https://www.readbyqxmd.com/read/28752115/acinar-to-ductal-metaplasia-induced-by-transforming-growth-factor-beta-facilitates-kras-g12d-driven-pancreatic-tumorigenesis
#20
Nicolas Chuvin, David F Vincent, Roxane M Pommier, Lindsay B Alcaraz, Johann Gout, Cassandre Caligaris, Karam Yacoub, Victoire Cardot, Elodie Roger, Bastien Kaniewski, Sylvie Martel, Celia Cintas, Sophie Goddard-Léon, Amélie Colombe, Julie Valantin, Nicolas Gadot, Emilie Servoz, Jennifer Morton, Isabelle Goddard, Anne Couvelard, Vinciane Rebours, Julie Guillermet, Owen J Sansom, Isabelle Treilleux, Ulrich Valcourt, Stéphanie Sentis, Pierre Dubus, Laurent Bartholin
BACKGROUND & AIMS: Transforming growth factor beta (TGFβ) acts either as a tumor suppressor or as an oncogene, depending on the cellular context and time of activation. TGFβ activates the canonical SMAD pathway through its interaction with the serine/threonine kinase type I and II heterotetrameric receptors. Previous studies investigating TGFβ-mediated signaling in the pancreas relied either on loss-of-function approaches or on ligand overexpression, and its effects on acinar cells have so far remained elusive...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
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