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https://www.readbyqxmd.com/read/29140547/islet-transplantation-as-safe-and-efficacious-method-to-restore-glycemic-control-and-to-avoid-severe-hypoglycemia-after-donor-organ-failure-in-pancreas-transplantation
#1
Philipp A Gerber, Michel Hochuli, Bara D Benediktsdottir, Richard A Zuellig, Oliver Tschopp, Michael Glenck, Olivier de Rougemont, Christian Oberkofler, Giatgen A Spinas, Roger Lehmann
The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas re-transplantation. 10 patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29138225/androgen-signaling-expands-%C3%AE-cell-mass-in-male-rats-and-%C3%AE-cell-androgen-receptor-is-degraded-under-high-glucose-conditions
#2
Naoki Harada, Yasuhiro Yoda, Yusuke Yotsumoto, Tatsuya Masuda, Yuji Takahashi, Takahiro Katsuki, Kenji Kai, Nobuaki Shiraki, Hiroshi Inui, Ryoichi Yamaji
A deficient pancreatic β-cell mass increases the risk of type 2 diabetes mellitus. Here, we investigated the effects of testosterone on the development of pancreatic β-cell mass in male rats. The β-cell mass of male rats castrated at 6 weeks of age was reduced to ~30% of that of control rats at 16 weeks of age, and castration caused glucose intolerance. Loss of β-cell mass occurred due to decreases in islet density/pancreas and β-cell cluster size. Castration was negatively associated with the number of Ki67-positive β-cells and positively associated with the number of TUNEL-positive β-cells...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29135679/characterization-of-the-human-pancreas-side-population-as-a-potential-reservoir-of-adult-stem-cells
#3
Petra Augstein, Thomas Loudovaris, Esther Bandala-Sanchez, Peter Heinke, Gaetano Naselli, Lily Lee, Wayne J Hawthorne, L Jorge Góñez, Alana M Neale, François Vaillant, Helen E Thomas, Thomas W Kay, Ilia Banakh, Leonard C Harrison
OBJECTIVES: The side population (SP) contains cells with stem cell/progenitor properties. Previously, we observed that the mouse pancreas SP expanded after pancreatic injury. We aimed to characterize the SP in human pancreas as a potential source of stem cells. METHODS: Human organ donor pancreata were fractionated into islets and exocrine tissue, enriched by tissue culture and dispersed into single cells. Cells were phenotyped by flow cytometry, and the SP was defined by efflux of fluorescent dye Hoechst 33342 visualized by ultraviolet excitation...
November 10, 2017: Pancreas
https://www.readbyqxmd.com/read/29133483/ctage5-deletion-in-pancreatic-%C3%AE-cells-impairs-proinsulin-trafficking-and-insulin-biogenesis-in-mice
#4
Junwan Fan, Yaqing Wang, Liang Liu, Hongsheng Zhang, Feng Zhang, Lei Shi, Mei Yu, Fei Gao, Zhiheng Xu
Proinsulin is synthesized in the endoplasmic reticulum (ER) in pancreatic β cells and transported to the Golgi apparatus for proper processing and secretion into plasma. Defects in insulin biogenesis may cause diabetes. However, the underlying mechanisms for proinsulin transport are still not fully understood. We show that β cell-specific deletion of cTAGE5, also known as Mea6, leads to increased ER stress, reduced insulin biogenesis in the pancreas, and severe glucose intolerance in mice. We reveal that cTAGE5/MEA6 interacts with vesicle membrane soluble N-ethyl-maleimide sensitive factor attachment protein receptor Sec22b...
November 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#5
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#6
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29111856/vascular-derived-connective-tissue-growth-factor-ctgf-is-critical-for-pregnancy-induced-%C3%AE-cell-hyperplasia-in-adult-mice
#7
Raymond C Pasek, Jennifer C Dunn, Joseph M Elsakr, Mounika Aramandla, Anveetha R Matta, Maureen Gannon
During pregnancy, maternal β cells undergo compensatory changes including hypertrophy, hyperplasia, and increased glucose-stimulated insulin secretion (GSIS). Failure of these adaptations to occur can result in gestational diabetes mellitus. The secreted protein, Connective tissue growth factor (Ctgf), is critical for normal β cell development and promotes regeneration after partial β cell ablation. During embryogenesis, Ctgf is expressed in pancreatic ducts, vasculature, and β cells. In the adult pancreas, Ctgf is expressed only in the vasculature...
November 7, 2017: Islets
https://www.readbyqxmd.com/read/29111283/pancreatic-islet-autonomous-effect-of-arsenic-on-insulin-secretion-through-endoplasmic-reticulum-stress-autophagy-pathway
#8
Wei Wu, Xiaofeng Yao, Liping Jiang, Qiaoting Zhang, Jie Bai, Tianming Qiu, Lei Yang, Ni Gao, Guang Yang, Xiaofang Liu, Min Chen, Xiance Sun
Inorganic arsenic is a worldwide environmental pollutant. Arsenic's relationship with the incidence of diabetes arouses concerns on its etiological mechanism. In this study, the glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets of As2O3-treated mice was significantly lower than that of control mice. It indicated that the effect of As2O3-inhibited GSIS was pancreatic islet-autonomous. The level of phospho-PERK (p-PERK), a biomarker of endoplasmic reticulum (ER) stress, in pancreas of As2O3-treated mice was increased significantly...
October 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#9
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29104117/characterization-of-somatostatin-receptors-and-associated-signaling-pathways-in-pancreas-of-r6-2-transgenic-mice
#10
Rishi K Somvanshi, Amrit Jhajj, Michael Heer, Ujendra Kumar
The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (β), glucagon (α) and somatostatin (δ) producing cells in the pancreatic islets of 11weeks old R6/2 Huntington's Disease transgenic (HD tg) and age-matched wild type (wt) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptophysin (SYP) in addition to signal transduction pathways associated with diabetes. In R6/2 mice, islets are relatively smaller in size, exhibit enhanced expression and nuclear inclusion of mHtt along with the loss of insulin, glucagon and somatostatin expression...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29097999/clostridium-butyricum-cgmcc0313-1-protects-against-autoimmune-diabetes-by-modulating-intestinal-immune-homeostasis-and-inducing-pancreatic-regulatory-t-cells
#11
Lingling Jia, Kai Shan, Li-Long Pan, Ninghan Feng, Zhuwu Lv, Yajun Sun, Jiahong Li, Chengfei Wu, Hao Zhang, Wei Chen, Julien Diana, Jia Sun, Yong Q Chen
Recent evidence indicates that indigenous Clostridium species induce colonic regulatory T cells (Tregs), and gut lymphocytes are able to migrate to pancreatic islets in an inflammatory environment. Thus, we speculate that supplementation with the well-characterized probiotics Clostridium butyricum CGMCC0313.1 (CB0313.1) may induce pancreatic Tregs and consequently inhibit the diabetes incidence in non-obese diabetic (NOD) mice. CB0313.1 was administered daily to female NOD mice from 3 to 45 weeks of age. The control group received an equal volume of sterile water...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#12
REVIEW
Yaxi Zhu, Qian Liu, Zhiguang Zhou, Yasuhiro Ikeda
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells...
November 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29095944/mif-inhibition-interferes-with-the-inflammatory-and-t-cell-stimulatory-capacity-of-nod-macrophages-and-delays-autoimmune-diabetes-onset
#13
Hannelie Korf, Laura Breser, Jelter Van Hoeck, Janet Godoy, Dana P Cook, Benoit Stijlemans, Elien De Smidt, Carolien Moyson, João Paulo Monteiro Carvalho Mori Cunha, Virginia Rivero, Conny Gysemans, Chantal Mathieu
Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D). However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF) and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas...
2017: PloS One
https://www.readbyqxmd.com/read/29093273/genetic-determinants-of-circulating-gip-and-glp-1-concentrations
#14
Peter Almgren, Andreas Lindqvist, Ulrika Krus, Liisa Hakaste, Emilia Ottosson-Laakso, Olof Asplund, Emily Sonestedt, Rashmi B Prasad, Esa Laurila, Marju Orho-Melander, Olle Melander, Tiinamaija Tuomi, Jens Juul Holst, Peter M Nilsson, Nils Wierup, Leif Groop, Emma Ahlqvist
The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29091932/essential-roles-of-aspartate-aminotransferase-1-and-vesicular-glutamate-transporters-in-%C3%AE-cell-glutamate-signaling-for-incretin-induced-insulin-secretion
#15
Naoya Murao, Norihide Yokoi, Kohei Honda, Guirong Han, Tomohide Hayami, Ghupurjan Gheni, Harumi Takahashi, Kohtaro Minami, Susumu Seino
Incretins (GLP-1 and GIP) potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS) that requires two critical processes: 1) generation of cytosolic glutamate through the malate-aspartate (MA) shuttle in glucose metabolism and 2) glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1), a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively), which participate in glutamate transport into secretory vesicles...
2017: PloS One
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#16
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073149/intrapancreatic-injection-of-human-bone-marrow-derived-mesenchymal-stem-stromal-cells-alleviates-hyperglycemia-and-modulates-the-macrophage-state-in-streptozotocin-induced-type-1-diabetic-mice
#17
Norimitsu Murai, Hirokazu Ohtaki, Jun Watanabe, Zhifang Xu, Shun Sasaki, Kazumichi Yagura, Seiji Shioda, Shoichiro Nagasaka, Kazuho Honda, Masahiko Izumizaki
Type 1 diabetes mellitus is a progressive disease caused by the destruction of pancreatic β-cells, resulting in insulin dependency and hyperglycemia. While transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been explored as an alternative therapeutic approach for diseases, the choice of delivery route may be a critical factor determining their sustainability. This study evaluated the effects of intrapancreatic and intravenous injection of human BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/29073082/transcription-factor-isx-mediates-the-cross-talk-between-diet-and-immunity
#18
Made Airanthi K Widjaja-Adhi, Grzegorz Palczewski, Kali Dale, Elizabeth A Knauss, Mary E Kelly, Marcin Golczak, Alan D Levine, Johannes von Lintig
The intestinal epithelium is a major site for the conversion of dietary β-carotene to retinaldehyde by the enzyme BCO1. The majority of retinaldehyde is further metabolized to retinol (vitamin A), esterified and packaged into triacylglycerol-rich chylomicrons for bodily distribution. Some serve on-site for the synthesis of retinoic acid, a hormone-like compound, which exerts pleiotropic and dominant effects on gastrointestinal immunity. We report here that the intestine-specific homeobox protein ISX is critical to control the metabolic flow of β-carotene through this important branching point of vitamin A metabolism...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29072081/cystic-pancreatic-neuroendocrine-tumors-cpnets-a-systematic-review-and-meta-analysis-of-case-series
#19
Luis Hurtado-Pardo, Javier A Cienfuegos, Miguel Ruiz-Canela, Pablo Panadero, Alberto Benito, José Luis Hernández Lizoain
Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87...
November 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29071956/-effect-of-electroacupuncture-at-weiwanxiashu-ex-b-3-on-islet-morphology-and-the-expression-of-pancreatic-glucagon-like-peptide-1-receptor-in-type-2-diabetes-rats
#20
Bing-Yan Cao, Rui Li, Huan-Huan Tian, Ning Jia, Xiao-Gang Hu, Yan-Jia Ma, Yue-Ying Wang
OBJECTIVE: To observe the effect of electroacupuncture (EA) on pancreatic glucagon-like peptide-1 receptor (GLP-1 R), pancreatic and duodenal homeobox 1 (PDX-1) protein expression and blood glucose in type 2 diabetes rats, so as to explore the underlying mechanism of EA treatment in improving type 2 diabetes. METHODS: Sprague-Dawley rats were randomly divided into blank control group, model group, "Weiwanxiashu" (EX-B 3) group, "Xinshu" (BL 15) group, and "Shenshu" (BL 23) group, 12 rats in each group...
April 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
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