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Islet production

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https://www.readbyqxmd.com/read/28731212/cross-validation-of-commercial-enzyme-linked-immunosorbent-assay-and-radioimmunoassay-for-porcine-c-peptide-concentration-measurements-in-non-human-primate-serum
#1
Sarah C Gresch, Lucas A Mutch, Jody L Janecek, Rebecca L Hegstad-Davies, Melanie L Graham
BACKGROUND: C-peptide concentration is widely used as a marker of insulin secretion and is especially relevant in evaluating islet graft function following transplantation, because its measurement is not confounded by the presence of exogenous insulin. To address the shortage of human islet donors, the use of porcine islets has been proposed as a possible solution and the stringent pig-to-non-human primate (NHP) model is often the most relevant for pre-clinical evaluation of the potential for diabetes reversal resulting from an islet xenograft...
July 21, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28727072/the-equine-glucose-dependent-insulinotropic-polypeptide-receptor-a-potential-therapeutic-target-for-insulin-dysregulation
#2
M H Kheder, M N Sillence, L M Bryant, M A de Laat
Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whether eGIPR can be blocked using a GIP antagonist not tested previously in horses, and to establish whether there is any association between GIP concentrations and body mass in this species...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28715390/mammalian-cell-encapsulation-in-alginate-beads-using-a-simple-stirred-vessel
#3
Corinne A Hoesli, Roger L J Kiang, Kamini Raghuram, René G Pedroza, Karen E Markwick, Antonio M R Colantuoni, James M Piret
Cell encapsulation in alginate beads has been used for immobilized cell culture in vitro as well as for immunoisolation in vivo. Pancreatic islet encapsulation has been studied extensively as a means to increase islet survival in allogeneic or xenogeneic transplants. Alginate encapsulation is commonly achieved by nozzle extrusion and external gelation. Using this method, cell-containing alginate droplets formed at the tip of nozzles fall into a solution containing divalent cations that cause ionotropic alginate gelation as they diffuse into the droplets...
June 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28710249/amyloid-precursor-protein-in-pancreatic-islets
#4
Joshua Kulas, Kendra Puig, Colin K Combs
The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque forming peptide in Alzheimer's disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well characterized consequence of type 1 and type 2 diabetes. In this study we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes...
July 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28702321/a-high-content-small-molecule-screen-identifies-novel-inducers-of-definitive-endoderm
#5
Alexander Korostylev, Pallavi U Mahaddalkar, Oliver Keminer, Kamyar Hadian, Kenji Schorpp, Philip Gribbon, Heiko Lickert
OBJECTIVES: Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can generate any given cell type in the human body. One challenge for cell-replacement therapy is the efficient differentiation and expansion of large quantities of progenitor cells from pluripotent stem cells produced under good manufacturing practice (GMP). FOXA2 and SOX17 double positive definitive endoderm (DE) progenitor cells can give rise to all endoderm-derived cell types in the thymus, thyroid, lung, pancreas, liver, and gastrointestinal tract...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28694505/presence-of-diabetes-autoantigens-in-extracellular-vesicles-derived-from-human-islets
#6
Craig P Hasilo, Sarita Negi, Isabelle Allaeys, Nathalie Cloutier, Alissa K Rutman, Marco Gasparrini, Éric Bonneil, Pierre Thibault, Éric Boilard, Steven Paraskevas
Beta-cell (β-cell) injury is the hallmark of autoimmune diabetes. However, the mechanisms by which autoreactive responses are generated in susceptible individuals are not well understood. Extracellular vesicles (EV) are produced by mammalian cells under normal and stressed physiological states. They are an important part of cellular communication, and may serve a role in antigen processing and presentation. We hypothesized that isolated human islets in culture produce EV that contain diabetes autoantigens (DAA) from these otherwise normal, non-diabetic donors...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684635/a-type-2-diabetes-associated-functional-regulatory-variant-in-a-pancreatic-islet-enhancer-at-the-adcy5-locus
#7
Tamara S Roman, Maren E Cannon, Swarooparani Vadlamudi, Martin L Buchkovich, Brooke N Wolford, Ryan P Welch, Mario A Morken, Grace J Kwon, Arushi Varshney, Romy Kursawe, Ying Wu, Anne U Jackson, Michael R Erdos, Johanna Kuusisto, Markku Laakso, Laura J Scott, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel, Karen L Mohlke
Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study (GWAS) identified loci. Variants associated with type 2 diabetes and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate cyclase 5 catalyzes the production of cyclic AMP, which is a second messenger molecule involved in cell signaling and pancreatic beta cell insulin secretion. We demonstrated that type 2 diabetes risk alleles are associated with decreased ADCY5 expression in human islets and examined candidate variants for regulatory function...
July 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28683308/microbial-host-co-metabolites-are-prodromal-markers-predicting-phenotypic-heterogeneity-in-behavior-obesity-and-impaired-glucose-tolerance
#8
Marc-Emmanuel Dumas, Alice R Rothwell, Lesley Hoyles, Thomas Aranias, Julien Chilloux, Sophie Calderari, Elisa M Noll, Noémie Péan, Claire L Boulangé, Christine Blancher, Richard H Barton, Quan Gu, Jane F Fearnside, Chloé Deshayes, Christophe Hue, James Scott, Jeremy K Nicholson, Dominique Gauguier
The influence of the gut microbiome on metabolic and behavioral traits is widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine (1)H-NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n = 50) and show that microbial-host co-metabolites are prodromal (i.e., early) markers predicting future divergence in metabolic (obesity and glucose homeostasis) and behavioral (anxiety and activity) outcomes with 94%-100% accuracy...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28672975/the-protective-effect-of-ginsenoside-rg1-on-aging-mouse-pancreas-damage-induced-by-d-galactose
#9
Zhaoying Dong, Mengxiong Xu, Jie Huang, Linbo Chen, Jieyu Xia, Xiongbin Chen, Rong Jiang, Lu Wang, Yaping Wang
The protective effect and mechanism of Ginsenoside Rg1 on aging mouse pancreas damaged by D-galactose (D-gal)-induced was studied. Two-month-old male C57BL/6J mice were randomly divided into three groups of 10 mice per group. The D-gal group of mice received hypodermic injection of D-gal (120 mg/kg/day) for 42 days; the Rg1+D-gal group of mice receiving D-gal + intraperitoneal injection Rg1 (40 mg/kg/day) for 27 days from the 16th day of D-gal replication; and the naïve group that constituted the normal control mice receiving the same dose of saline instead of the drug...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28672010/fibroblasts-accelerate-islet-revascularization-and-improve-long-term-graft-survival-in-a-mouse-model-of-subcutaneous-islet-transplantation
#10
Marcos Perez-Basterrechea, Manuel Martinez Esteban, Maria Alvarez-Viejo, Tania Fontanil, Santiago Cal, Marta Sanchez Pitiot, Jesus Otero, Alvaro Jesus Obaya
Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors...
2017: PloS One
https://www.readbyqxmd.com/read/28663189/erratum-national-institutes-of-health-sponsored-clinical-islet-transplantation-consortium-phase-3-trial-manufacture-of-a-complex-cellular-product-at-eight-processing-facilities-diabetes-2016-65-3418-3428
#11
Camillo Ricordi, Julia S Goldstein, A N Balamurugan, Gregory L Szot, Tatsuya Kin, Chengyang Liu, Christine W Czarniecki, Barbara Barbaro, Nancy D Bridges, Jose Cano, William R Clarke, Thomas L Eggerman, Lawrence G Hunsicker, Dixon B Kaufman, Aisha Khan, David-Erick Lafontant, Elina Linetsky, Xunrong Luo, James F Markmann, Ali Naji, Olle Korsgren, Jose Oberholzer, Nicole A Turgeon, Daniel Brandhorst, Andrew S Friberg, Ji Lei, Ling-Jia Wang, Joshua J Wilhelm, Jamie Willits, Xiaomin Zhang, Bernhard J Hering, Andrew M Posselt, Peter G Stock, A M James Shapiro
No abstract text is available yet for this article.
June 29, 2017: Diabetes
https://www.readbyqxmd.com/read/28655753/the-thermodynamic-basis-of-glucose-stimulated-insulin-release-a-model-of-the-core-mechanism
#12
David F Wilson, Abigail T J Cember, Franz M Matschinsky
A model for glucose sensing by pancreatic β-cells is developed and compared with the available experimental data. The model brings together mathematical representations for the activities of the glucose sensor, glucokinase, and oxidative phosphorylation. Glucokinase produces glucose 6-phosphate (G-6-P) in an irreversible reaction that determines glycolytic flux. The primary products of glycolysis are NADH and pyruvate. The NADH is reoxidized and the reducing equivalents transferred to oxidative phosphorylation by the glycerol phosphate shuttle, and some of the pyruvate is oxidized by pyruvate dehydrogenase and enters the citric acid cycle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28655312/transplantation-of-human-fetal-pancreatic-progenitor-cells-ameliorates-renal-injury-in-streptozotocin-induced-diabetic-nephropathy
#13
Yongwei Jiang, Wenjian Zhang, Shiqing Xu, Hua Lin, Weiguo Sui, Honglin Liu, Liang Peng, Qing Fang, Li Chen, Jinning Lou
BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem. OBJECTIVE: To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM...
June 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28649880/understanding-type-1-diabetes-through-proteomics
#14
Inne Crèvecoeur, Saurabh Vig, Chantal Mathieu, Lut Overbergh
Auto-immunity against pancreatic beta-cells leads to an absolute shortage of the hormone insulin, resulting in hyperglycemia and the onset of type 1 diabetes (T1D). Proteomic approaches have been used to elucidate the mechanisms of beta-cell dysfunction and death. Areas covered: In the present review, we discuss discoveries in the beta-cell proteome that have contributed to better insights in the role of the beta-cell in T1D. Techniques, such as 2D-DIGE and MALDI imaging, together with new approaches for sample preparation, including laser capture microdissection and immunopeptidomics, have resulted in novel mechanistic insights in the pathogenesis of T1D...
June 28, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28640379/comparative-and-correlative-assessments-of-cytokine-complement-and-antibody-patterns-in-pediatric-type-1-diabetes
#15
M Abdel-Latif, A A Abdel-Moneim, M H El-Hefnawy, R G Khalil
One of the most widespread and effective environmental factors is the infection with enteroviruses (EVs) which accelerate β - cell destruction in type 1 diabetes (T1D). This study represented a comparison between diabetic EV(+) and EV- children as well as correlation analysis between autoantibodies, T1D markers, cytokines, complement activation products and anti- coxsackievirus (CV) IgG. EV RNA was detected in Egyptian children with T1D (26.2%) and healthy controls (0%). Detection of anti - CV IgG in T1D - EV(+) resulted in 64% positivity...
June 22, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28632821/encapsulated-islet-transplantation-where-do-we-stand
#16
Vijayaganapathy Vaithilingam, Sumeet Bal, Bernard E Tuch
Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO)...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632819/enzyme-development-for-human-islet-isolation-five-decades-of-progress-or-stagnation
#17
Daniel Brandhorst, Heide Brandhorst, Paul R V Johnson
In comparison to procedures used for the separation of individual cell types from other organs, the process of human pancreatic islet isolation aims to digest the pancreatic exocrine matrix completely without dispersing the individual cells within the endocrine cell cluster. This objective is unique within the field of tissue separation, and outlines the challenge of islet isolation to balance two opposing priorities. Although significant progress has been made in the characterization and production of enzyme blends for islet isolation, there are still numerous areas which require improvement...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28630088/the-islet-resident-macrophage-is-in-an-inflammatory-state-and-senses-microbial-products-in-blood
#18
Stephen T Ferris, Pavel N Zakharov, Xiaoxiao Wan, Boris Calderon, Maxim N Artyomov, Emil R Unanue, Javier A Carrero
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of 3-wk-old non-obese diabetic (NOD), NOD.Rag1(-/-), and B6.g7 mice. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II at both the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them...
June 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28616498/xenotransplantation-a-special-case-of-one-health
#19
REVIEW
Joachim Denner
The chronic shortage of human transplants to treat tissue and organ failure has led to the development of xenotransplantation, the transplantation of cells, tissues and organs from another species to human recipients. For a number of reasons, pigs are best suited as donor animals. Successful, routine xenotransplantation would have an enormous impact on the health of the human population, including the young, who sometimes require a replacement organ or islet cells, but especially the elderly, who more often suffer the consequences of organ failure...
June 2017: One Health
https://www.readbyqxmd.com/read/28611472/cd11a-icam-1-blockade-combined-with-il-2-targeting-therapy-causes-a-paradoxical-acceleration-of-type-1-diabetes
#20
Ekua W Brenu, Timothy J Bartley, Casey M Wright, Emma Hamilton-Williams
Enhancement of regulatory T cell (Treg) function is the goal of many immunotherapies aimed at treating type 1 diabetes (T1D). The use of IL-2 is hindered by its effects on other populations such as effector T cells and NK cells. Combination therapies aimed at suppressing effector T cells while using IL-2 to expand Tregs could be beneficial and have been trialed in T1D patients. We have investigated a combination therapy using IL-2 and αCD11a blocking antibody to simultaneously expand Tregs and suppress the activation and migration of autoreactive T cells...
June 14, 2017: Immunology and Cell Biology
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