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https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#1
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#2
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28190419/seaweed-extracts-and-galacto-oligosaccharides-improve-intestinal-health-in-pigs-following-salmonella-typhimurium-challenge
#3
M A Bouwhuis, M J McDonnell, T Sweeney, A Mukhopadhya, C J O'Shea, J V O'Doherty
Pork and pork products are recognised as vehicles of Salmonella Typhimurium infection in humans. Seaweed-derived polysaccharides (SWE) and galacto-oligosaccharides (GOS) have shown to exhibit antimicrobial, prebiotic and immunomodulatory activity. The objective of this study was to assess the effects of dietary GOS and SWE supplementation on reducing S. Typhimurium numbers and intestinal inflammation in vivo. In total, 30 pigs (n=10/treatment, BW 30.9 kg) were randomly assigned to three dietary treatments: (1) basal diet; (2) basal diet+2...
February 13, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28186705/current-and-future-perspectives-on-alginate-encapsulated-pancreatic-islet
#4
Berit L Strand, Abba E Coron, Gudmund Skjak-Braek
Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long-term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long-term function of the graft in humans...
February 2, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28182770/biochemical-and-biophysical-investigations-of-the-interaction-between-human-glucokinase-and-pro-apoptotic-bad
#5
Alix Rexford, Diego A R Zorio, Brian G Miller
The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD...
2017: PloS One
https://www.readbyqxmd.com/read/28181140/real-architecture-for-3d-tissue-raft%C3%A2-culture-system-improves-viability-and-maintains-insulin-and-glucagon-production-of-mouse-pancreatic-islet-cells
#6
Gabor J Szebeni, Zsuzsanna Tancos, Liliana Z Feher, Robert Alfoldi, Julianna Kobolak, Andras Dinnyes, Laszlo G Puskas
There is an unmet medical need for the improvement of pancreatic islet maintenance in culture. Due to restricted donor availability it is essential to ameliorate islet viability and graft engraftment. The aim of this study was to compare the standard tissue culture techniques with the advanced Real Architecture For 3D Tissue (RAFT™) culture system in terms of viability and hormone production. Here, we first report that islets embedded in RAFT™ collagen type I advanced tissue culture system maintain their tissue integrity better than in monolayer and suspension cultures...
February 8, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28180948/tributyltin-exposure-at-noncytotoxic-doses-dysregulates-pancreatic-%C3%AE-cell-function-in-vitro-and-in-vivo
#7
Ya-Wen Chen, Kuo-Cheng Lan, Jing-Ren Tsai, Te-I Weng, Ching-Yao Yang, Shing-Hwa Liu
Tributyltin (TBT) is an endocrine disruptor. TBT can be found in food and in human tissues and blood. Several animal studies revealed that organotins induced diabetes with decreased insulin secretion. The detailed effect and mechanism of TBT on pancreatic β-cell function still remain unclear. We investigated the effect and mechanism of TBT exposure at noncytotoxic doses relevant to human exposure on β-cell function in vitro and in vivo. The β-cell-derived RIN-m5F cells and pancreatic islets from mouse and human were treated with TBT (0...
February 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28174291/local-sphingosine-kinase-1-activity-improves-islet-transplantation
#8
Darling Rojas-Canales, Daniella Penko, Kay K Myo Min, Kate A Parham, Heshan Peiris, Rainer V Haberberger, Stuart M Pitson, Chris Drogemuller, Damien J Keating, Shane T Grey, Patrick T Coates, Claudine S Bonder, Claire F Jessup
Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28163291/production-of-insulin-like-growth-factor-ii-in-hepatocellular-carcinoma-with-recurrent-hypoglycemia-a-case-report
#9
Rieko Nakata, Hirokazu Kadoya, Naoki Sugimura, Takayuki Katsuno, Kazuki Aomatsu, Tsuyoshi Hayakawa, Sawako Uchida-Kobayashi, Tetsuo Arakawa, Hideaki Miwa
A 35-year-old woman, who was an HBV carrier, complained of fever for 2 weeks, and thus, she was admitted in our hospital. Both serum AFP and PIVKA-II levels were abnormally high, and an abdominal enhanced CT revealed the presence of multiple masses in both lobes of the liver. She was diagnosed with hepatocellular carcinoma (T4, N0, M0, and Vp4) and was treated with transcatheter arterial infusion chemotherapy. On the 4th day of her illness, her serum glucose level was 26mg/dl. Glucose infusion and intravenous hyperalimentation were not effective, and she experienced repeated hypoglycemic attacks...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28153469/evaluation-of-motor-neuron-differentiation-potential-of-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-in-vitro
#10
Behnam Yousefi, Davood Sanooghi, Faezeh Faghihi, Mohammad Taghi Joghataei, Nourahmad Latifi
Many people suffer from spinal cord injuries annually. These deficits usually threaten the quality of life of patients. As a postpartum medically waste product, human Umbilical Cord Blood (UCB) is a rich source of stem cells with self- renewal properties and neural differentiation capacity which made it useful in regenerative medicine. Since there is no report on potential of human umbilical cord blood-derived mesenchymal stem cells into motor neurons, we set out to evaluate the differentiation properties of these cells into motor neuron-like cells through administration of Retinoic Acid(RA), Sonic Hedgehog(Shh) and BDNF using a three- step in vitro procedure...
January 31, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28150721/early-life-antibiotic-exposure-affects-pancreatic-islet-development-and-metabolic-regulation
#11
Jiaying Li, Kaiyuan Yang, Tingting Ju, Tracy Ho, Catharine A McKay, Yanhua Gao, Shay K Forget, Stephanie R Gartner, Catherine J Field, Catherine B Chan, Benjamin P Willing
Childhood antibiotic exposure has been recently linked with increased risk of metabolic disease later in life. A better understanding of this association would potentially provide strategies to reduce the childhood chronic disease epidemic. Therefore, we explored the underlying mechanisms using a swine model that better mimics human infants than rodents, and demonstrated that early life antibiotic exposure affects glucose metabolism 5 weeks after antibiotic withdrawal, which was associated with changes in pancreatic development...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28146100/echovirus-6-infects-human-exocrine-and-endocrine-pancreatic-cells-and-induces-pro-inflammatory-innate-immune-response
#12
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/28137793/increase-in-pancreatic-proinsulin-and-preservation-of-beta-cell-mass-in-autoantibody-positive-donors-prior-to-type-1-diabetes-onset
#13
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/28130838/production-of-high-quality-islets-from-goettingen-minipigs-choice-of-organ-preservation-solution-donor-pool-and-optimal-cold-ischemia-time
#14
Anja Steffen, Thomas Kiss, Janine Schmid, Undine Schubert, Sophie Heinke, Susann Lehmann, Stefan Bornstein, Barbara Ludwig, Stefan Ludwig
BACKGROUND: The transplantation of porcine islets into man might soon become reality for patients with type 1 diabetes mellitus. Therefore, porcine islets of high quality and quantity, and a scalable isolation process with strict quality control will be an unconditional prerequisite to enable the best possible transplantation graft. In this study, we provide a comparative study evaluating islet isolation outcome and in vitro survival based upon donor age, organ preservation solution (OPS), and cold ischemia time (CIT)...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28122254/an-alpha-beta-of-pancreatic-islet-microribonucleotides
#15
REVIEW
Louise Torp Dalgaard, Lena Eliasson
MicroRNAs (miRNAs) are cellular, short, non-coding ribonucleotides acting as endogenous posttranscriptional repressors following incorporation in the RNA-induced silencing complex. Despite being chemically and mechanistically very similar, miRNAs exert a multitude of different cellular effects by acting on mRNA species, whose gene-products partake in a wide array of processes. Here, the aim was to review the knowledge of miRNA expression and action in the islet of Langerhans. We have focused on: 1) physiological consequences of islet or beta cell specific inhibition of miRNA processing, 2) mechanisms regulating processing of miRNAs in islet cells, 3) presence and function of miRNAs in alpha versus beta cells - the two main cell types of islets, and 4) miRNA mediators of beta cell decompensation...
January 22, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28109957/adoptive-transfer-of-mrna-transfected-t-cells-redirected-against-diabetogenic-cd8%C3%A2-t-cells-can-prevent-diabetes
#16
Sigal Fishman, Mark D Lewis, L Khai Siew, Evy De Leenheer, Dimitri Kakabadse, Joanne Davies, Doron Ziv, Alon Margalit, Nathan Karin, Gideon Gross, F Susan Wong
Chimeric major histocompatibility complex (MHC) molecules supplemented with T cell receptor (TCR) signaling motifs function as activation receptors and can redirect gene-modified T cells against pathogenic CD8 T cells. We have shown that β2 microglobulin (β2m) operates as a universal signaling component of MHC-I molecules when fused with the CD3-ζ chain. Linking the H-2K(d)-binding insulin B chain peptide insulin B chain, amino acids 15-23 (InsB15-23) to the N terminus of β2m/CD3-ζ, redirected polyclonal CD8 T cells against pathogenic CD8 T cells in a peptide-specific manner in the non-obese diabetic (NOD) mouse...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28101570/inhibition-of-tlr4-protects-rat-islets-against-lipopolysaccharide-induced-dysfunction
#17
Xiao Wang, Qin Min Ge, Fan Bian, Yan Dong, Chun Mei Huang
Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098903/vitexin-alleviates-lipopolysaccharide%C3%A2-induced-islet-cell-injury-by-inhibiting-hmgb1-release
#18
Feifei Wang, Jiajing Yin, Yujin Ma, Hongwei Jiang, Yanbo Li
Diabetes mellitus (DM) is a chronic metabolic disease, where the predominant pathogenesis is pancreatic β‑cells dysfunction or injury. It has been well established that inflammation leads to a gradual exhaustion of pancreatic β‑cell function with decreased β‑cell mass likely resulting from pancreatic β‑cells apoptosis or death. Vitexin, a major bioactive flavonoid compound in plants has numerous pharmacological properties, including antioxidant, anti‑inflammatory and antimyeloperoxidase. Whether vitexin can protect pancreatic β‑cells against lipopolysaccharide (LPS)‑induced pro‑inflammatory cytokine production and apoptosis has received little attention...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28069642/alpha-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#19
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that alpha-1 antitrypsin (AAT, Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared to mice treated with saline...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28025655/targets-and-probes-for-non-invasive-imaging-of-%C3%AE-cells
#20
REVIEW
Andreas Jodal, Roger Schibli, Martin Béhé
β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements...
December 26, 2016: European Journal of Nuclear Medicine and Molecular Imaging
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