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Islet production

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https://www.readbyqxmd.com/read/28332581/elevated-mir-130a-mir130b-mir-152-expression-reduces-intracellular-atp-levels-in-the-pancreatic-beta-cell
#1
Jones K Ofori, Vishal A Salunkhe, Annika Bagge, Neelanjan Vishnu, Mototsugu Nagao, Hindrik Mulder, Claes B Wollheim, Lena Eliasson, Jonathan L S Esguerra
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325871/progression-of-type-1-diabetes-from-the-prediabetic-stage-is-controlled-by-interferon-%C3%AE-signaling
#2
Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28317340/production-of-pancreatic-progenitor-cells-from-human-induced-pluripotent-stem-cells-using-a-three-dimensional-suspension-bioreactor-system
#3
Yuichiro Mihara, Katsuhisa Matsuura, Yoshihiro Sakamoto, Teruo Okano, Norihiro Kokudo, Tatsuya Shimizu
Islet replacement is a promising strategy for the treatment of patients with type 1 diabetes and patients who have undergone total pancreatectomy. Recent progress in cellular reprogramming technology may allow the transplantation of a patient's own pancreatic cells. Although many studies have reported the differentiation of pancreatic progenitor cells from mouse and human pluripotent stem cells (PSCs), obtaining sufficient cell numbers for clinical applications remains problematic. Here, we describe the mass production of human pancreatic progenitor cells from human induced (i)PSCs using a three-dimensional suspension bioreactor system...
March 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28290605/transplantation-of-betatrophin-expressing-adipose-derived-mesenchymal-stem-cells-induces-%C3%AE-cell-proliferation-in-diabetic-mice
#4
Liang-Liang Sun, Tian-Jin Liu, Limei Li, Wei Tang, Jun-Jie Zou, Xiang-Fang Chen, Jiao-Yang Zheng, Bei-Ge Jiang, Yong-Quan Shi
Recent progress in regenerative medicine has suggested that mesenchymal stem cell (MSC)-based therapy is a novel potential cure for diabetes. Betatrophin is a newly identified hormone that can increase the production and expansion of insulin-secreting β-cells when administered to mice. In this study, we evaluated the effect of betatrophin overexpression by human adipose-derived MSCs (ADMSCs) by in vitro experiments, as well as following their transplantation into a mice with streptozotocin (STZ)-induced diabetes...
March 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289997/innovative-microcapsules-for-pancreatic-%C3%AE-cells-harvested-from-mature-double-transgenic-mice-cell-imaging-viability-induced-glucose-stimulated-insulin-measurements-and-proinflammatory-cytokines-analysis
#5
Armin Mooranian, Ryu Tackechi, Emma Jamieson, Grant Morahan, Hani Al-Salami
PURPOSE: Recently we demonstrated that microencapsulation of a murine pancreatic β-cell line using an alginate-ursodeoxycholic acid (UDCA) matrix produced microcapsules with good stability and cell viability. In this study, we investigated if translation of this formulation to microencapsulation of primary β-cells harvested from mature double-transgenic healthy mice would also generate stable microcapsules with good cell viability. METHODS: Islets of Langerhans were isolated from Ngn3-GFP/RIP-DsRED mice by intraductal collagenase P digestion and density gradient centrifugation, dissociated into single cells and the β-cell population purified by Fluorescence Activated Cell Sorting...
March 13, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28287098/the-redox-environment-triggers-conformational-changes-and-aggregation-of-hiapp-in-type-ii-diabetes
#6
Diana C Rodriguez Camargo, Konstantinos Tripsianes, Katalin Buday, Andras Franko, Christoph Göbl, Christoph Hartlmüller, Riddhiman Sarkar, Michaela Aichler, Gabriele Mettenleiter, Michael Schulz, Annett Böddrich, Christian Erck, Henrik Martens, Axel Karl Walch, Tobias Madl, Erich E Wanker, Marcus Conrad, Martin Hrabě de Angelis, Bernd Reif
Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28280903/microrna-21-targets-bcl2-mrna-to-increase-apoptosis-in-rat-and-human-beta-cells
#7
Emily K Sims, Alexander J Lakhter, Emily Anderson-Baucum, Tatsuyoshi Kono, Xin Tong, Carmella Evans-Molina
AIMS/HYPOTHESIS: The role of beta cell microRNA (miR)-21 in the pathophysiology of type 1 diabetes has been controversial. Here, we sought to define the context of beta cell miR-21 upregulation in type 1 diabetes and the phenotype of beta cell miR-21 overexpression through target identification. METHODS: Islets were isolated from NOD mice and mice treated with multiple low doses of streptozotocin, as a mouse model of diabetes. INS-1 832/13 beta cells and human islets were treated with IL-1β, IFN-γ and TNF-α to mimic the milieu of early type 1 diabetes...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28280376/single-donor-islet-transplantation-in-type-1-diabetes-patient-selection-and-special-considerations
#8
REVIEW
Jacob A Tatum, Max O Meneveau, Kenneth L Brayman
Type 1 diabetes mellitus is an autoimmune disorder of the endocrine pancreas that currently affects millions of people in the United States. Although the disease can be managed with exogenous insulin administration, the ultimate cure for the condition lies in restoring a patient's ability to produce their own insulin. Islet cell allotransplantation provides a means of endogenous insulin production. Though far from perfected, islet transplants are now a proven treatment for type 1 diabetics. However, proper patient selection is critical for achieving optimal outcomes...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28277987/endoc-%C3%AE-h1-cells-display-increased-sensitivity-to-sodium-palmitate-when-cultured-in-dmem-f12-medium
#9
Camilla Krizhanovskii, Hjalti Kristinsson, Andris Elksnis, Xuan Wang, Hamid Gavali, Peter Bergsten, Raphael Scharfmann, Nils Welsh
Aims - Human pancreatic islets are known to die in response to the free fatty acid of sodium palmitate when cultured in vitro. This is in contrast to EndoC-βH1 cells, which in our hands are not sensitive to the cell death-inducing effects sodium palmitate, making these cells seemingly unsuitable for lipotoxicity studies. However, the EndoC-βH1 cells are routinely cultured in a nutrient mixture based on Dulbecco's Modified Eagle Medium (DMEM), which may not be the optimal choice for studies dealing with lipotoxicity...
February 28, 2017: Islets
https://www.readbyqxmd.com/read/28255273/increase-in-peripheral-blood-intermediate-monocytes-is-associated-with-the-development-of-recent-onset-type-1-diabetes-mellitus-in-children
#10
Xiaoya Ren, Wenjun Mou, Chang Su, Xi Chen, Hui Zhang, Bingyan Cao, Xiaoqiao Li, Di Wu, Xin Ni, Jingang Gui, Chunxiu Gong
Monocytes play important roles in antigen presentation and cytokine production to achieve a proper immune response, and are therefore largely implicated in the development and progression of autoimmune diseases. The aim of this study was to analyze the change in the intermediate (CD14+CD16+) monocyte subset in children with recent-onset type 1 diabetes mellitus (T1DM) and its possible association with clinical parameters reflecting islet β-cell dysfunction. Compared with age- and sex-matched healthy controls, intermediate monocytes were expanded in children with T1DM, which was positively associated with hemoglobin A1C and negatively associated with serum insulin and C-peptide...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28255157/role-of-high-mobility-group-box-1-hmgb1-in-transplantation-of-rat-pancreatic-islets
#11
Seonghee Jeong, Song Lee, Chan Mee-Lee, In Kyong Shim, Song-Cheol Kim
BACKGROUND The potential role of tissue damage factor high-mobility group box 1 (HMGB1) in islet cell transplantation is poorly understood. We investigated the role of HMGB1 in pancreatic islet cell isolation and culture in vitro and after pancreatic islet cell transplantation into diabetic nude mice in vivo. MATERIAL AND METHODS To generate damaged islets, isolated islets were treated with 1 mg/mL lipopolysaccharide (LPS). Some islets were pretreated with a neutralizing anti-HMGB1 antibody before LPS treatment to investigate the effect of HMGB1 on isolated islets damaged by LPS...
March 3, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28238527/interferon-alpha-impairs-insulin-production-in-human-beta-cells-via-endoplasmic-reticulum-stress
#12
Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28237718/endogenous-beta-cell-cart-regulates-insulin-secretion-and-transcription-of-beta-cell-genes
#13
L Shcherbina, A Edlund, J L S Esguerra, M Abels, Y Zhou, E Ottosson-Laakso, C B Wollheim, O Hansson, L Eliasson, N Wierup
Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing...
February 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28223801/phytobioactive-compound-based-nanodelivery-systems-for-the-treatment-of-type-2-diabetes-mellitus-current-status
#14
REVIEW
Palanivel Ganesan, Palanisamy Arulselvan, Dong-Kug Choi
Type 2 diabetes mellitus (T2DM) is a major chronic disease that is prevalent worldwide, and it is characterized by an increase in blood glucose, disturbances in the metabolism, and alteration in insulin secretion. Nowadays, food-based therapy has become an important treatment mode for type 2 diabetes, and phytobioactive compounds have gained an increasing amount of attention to this end because they have an effect on multiple biological functions, including the sustained secretion of insulin and regeneration of pancreatic islets cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28222054/ucp2-expression-is-increased-in-pancreas-from-brain-dead-donors-and-involved-in-cytokine-induced-%C3%AE-cells-apoptosis
#15
Leticia A Brondani, Tatiana H Rech, Gabriela Boelter, Andrea C Bauer, Cristiane B Leitão, Décio L Eizirik, Daisy Crispim
BACKGROUND: Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial...
March 2017: Transplantation
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-up-regulates-programmed-cell-death-protein-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#16
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 T-cell receptor 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...
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
#17
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
#18
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
#19
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
#20
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
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