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https://www.readbyqxmd.com/read/28109023/intraportal-islet-transplantation-the-impact-of-the-liver-micro-environment
#1
REVIEW
Vaihere Delaune, Thierry Berney, Stéphanie Lacotte, Christian Toso
The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver micro-environment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver micro-environment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood mediated inflammatory reaction (IBMIR), the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets...
January 21, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28108610/circulating-cxcr5-pd-1-icos-follicular-t-helper-cells-are-increased-close-to-the-diagnosis-of-type-1-diabetes-in-children-with-multiple-autoantibodies
#2
Tyyne Viisanen, Emmi-Leena Ihantola, Kirsti Näntö-Salonen, Heikki Hyöty, Noora Nurminen, Jenni Selvenius, Auni Juutilainen, Leena Moilanen, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108533/noncerebral-amyloidoses-aspects-on-seeding-cross-seeding-and-transmission
#3
Gunilla T Westermark, Marcus Fändrich, Katarzyna Lundmark, Per Westermark
More than 30 proteins form amyloid in humans, most of them outside of the brain. Deposition of amyloid in extracerebral tissues is very common and seems inevitable for an aging person. Most deposits are localized, small, and probably without consequence, but in some instances, they are associated with diseases such as type 2 diabetes. Other extracerebral amyloidoses are systemic, with life-threatening effects on the heart, kidneys, and other organs. Here, we review how amyloid may spread through seeding and whether transmission of amyloid diseases may occur between humans...
January 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#4
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28106108/isl2b-regulates-anterior-second-heart-field-development-in-zebrafish
#5
Hagen R Witzel, Sirisha Cheedipudi, Rui Gao, Didier Y R Stainier, Gergana D Dobreva
After initial formation, the heart tube grows by addition of second heart field progenitor cells to its poles. The transcription factor Isl1 is expressed in the entire second heart field in mouse, and Isl1-deficient mouse embryos show defects in arterial and venous pole development. The expression of Isl1 is conserved in zebrafish cardiac progenitors; however, Isl1 is required for cardiomyocyte differentiation only at the venous pole. Here we show that Isl1 homologues are expressed in specific patterns in the developing zebrafish heart and play distinct roles during cardiac morphogenesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104122/role-of-natural-killer-cells-in-the-innate-immune-system-after-intraportal-islet-transplantation-in-mice
#6
Y Saeki, K Ishiyama, N Ishida, Y Tanaka, H Ohdan
BACKGROUND: Both liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation. METHODS: To investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d(-/-) diabetic mice and NK cell-depleted CD1d(-/-) diabetic mice...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28103022/discovery-of-a-novel-series-of-orally-bioavailable-and-cns-penetrant-glucagon-like-peptide-1-receptor-glp-1r-non-competitive-antagonists-based-on-a-1-3-disubstituted-7-aryl-5-5-bis-trifluoromethyl-5-8-dihydropyrimido-4-5-d-pyrimidine-2-4-1h-3h-dione-core
#7
Kellie D Nance, Emily L Days, C David Weaver, Anastasia Coldren, Tiffany D Farmer, Hyekyung P Cho, Colleen M Niswender, Anna L Blobaum, Kevin D Niswender, Craig W Lindsley
A duplexed, functional multi-addition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) non-competitive antagonist. Antagonist 5d not only blocked Exendin-4-stimulated insulin release in islets, but also lowered insulin levels while increasing blood glucose in vivo.
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28101570/inhibition-of-tlr4-protects-rat-islets-against-lipopolysaccharide-induced-dysfunction
#8
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/28101160/facile-mechanical-shaking-method-is-an-improved-isolation-approach-for-islet-preparation-and-transplantation
#9
Nina Yin, Tao Chen, Yuling Yu, Yongming Han, Fei Yan, Zhou Zheng, Zebin Chen
Successful islet isolation is crucial for islet transplantation and cell treatment for type 1 diabetes. Current isolation methods are able to obtain 500-1,000 islets per rat, which results in a waste of ≥50% of total islets. In the present study, a facile mechanical shaking method for improving islet yield (up to 1,500 per rat) was developed and summarized, which was demonstrated to be more effective than the existing well-established stationary method. The present results showed that isolated islets have a maximum yield of 1,326±152 when shaking for 15 min for the fully-cannulated pancreas...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#10
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
January 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28100774/loss-of-cyclin-dependent-kinase-2-in-the-pancreas-links-primary-%C3%AE-cell-dysfunction-to-progressive-depletion-of-%C3%AE-cell-mass-and-diabetes
#11
So Yoon Kim, Ji-Hyeon Lee, Matthew J Merrins, Oksana Gavrilova, Xavier Bisteau, Philipp Kaldis, Leslie S Satin, Sushil G Rane
The failure of pancreatic islet β-cells is a major contributor to the etiology of Type 2 diabetes. β-cell dysfunction and declining β-cell mass are two mechanisms that contribute to this failure, although it is unclear if they are molecularly linked. Here, we show that the cell cycle regulator, cyclin-dependent kinase 2 (Cdk2), couples primary β-cell dysfunction to the progressive deterioration of β-cell mass in diabetes. Mice with pancreas-specific deletion of Cdk2 are glucose intolerant primarily due to defects in glucose-stimulated insulin secretion...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100476/chronic-anemic-hypoxemia-attenuates-glucose-stimulated-insulin-secretion-in-fetal-sheep
#12
Joshua S Benjamin, Christine B Culpepper, Laura D Brown, Stephanie R Wesolowski, Sonnet S Jonker, Melissa Ann Davis, Sean W Limesand, Randall B Wilkening, William W Hay, Paul J Rozance
Fetal insulin secretion is inhibited by acute hypoxemia. The relationship between prolonged hypoxemia and insulin secretion, however, is less well defined. To test the hypothesis that prolonged fetal hypoxemia impairs insulin secretion, studies were performed in sheep fetuses that were bled to anemic conditions for 9 ± 0 days (anemic, n=19) and compared to control fetuses (n=15). Arterial hematocrit and oxygen content were 34% and 52% lower, respectively, in anemic vs. control fetuses (P<0.0001). Plasma glucose concentrations were 21% higher in the anemic group (P<0...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28099262/angiotensin-ii-type-2-receptor-activation-with-compound-21-augments-islet-function-and-regeneration-in-streptozotocin-induced-neonatal-rats-and-human-pancreatic-progenitor-cells
#13
Lin Wang, Yi Wang, Xing Yu Li, Po Sing Leung
OBJECTIVES: We investigated the effects of compound 21 (C21), a nonpeptide angiotensin II type 2 receptor agonist, on islet cell function and survival in streptozotocin (STZ)-treated neonatal rats and human pancreatic progenitor cells. METHODS: Neonatal rats were randomized into 5 groups, including a control, an STZ (100 mg/kg, intraperitoneally), and 3 STZ + C21 (0.25, 0.5, and 1 mg/kg per day for 7 days, intraperitoneally) groups. Body weight and blood glucose were monitored daily...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28099206/is-a-%C3%AE-cell-a-%C3%AE-cell
#14
Chaoxing Yang, Feorillo Galivo, Craig Dorrell
PURPOSE OF REVIEW: This report examines recent publications identifying phenotypic and functional heterogeneity among pancreatic β cells and investigating their potential roles in normal and abnormal islet function. The development of new methods and tools for the study of individual islet cells has produced a surge of interest in this topic. RECENT FINDINGS: Studies of β cell maturation and pregnancy-induced proliferation have identified changes in serotonin and transcription factors SIX2/3 expression as markers of temporal heterogeneity...
January 17, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28099204/narrowing-in-on-the-anti-%C3%AE-cell-specific-t-cells-looking-where-the-action-is
#15
Sally C Kent, Jenny Aurielle B Babon
PURPOSE OF THE REVIEW: By necessity, the vast majority of information we have on autoreactive T cells in human type 1 diabetes (T1D) has come from the study of peripheral blood of donors with T1D. It is not clear how representative the peripheral autoreactive T-cell repertoire is of the autoreactive T cells infiltrating the islets in T1D. We will summarize and discuss what is known of the immunohistopathology of insulitis, the T-cell receptor repertoire expressed by islet-infiltrating T cells, and the autoreactivity and function of islet-infiltrating T cells in T1D...
January 17, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28098903/vitexin-alleviates-lipopolysaccharide%C3%A2-induced-islet-cell-injury-by-inhibiting-hmgb1-release
#16
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/28098405/shielding-engineered-islets-with-mesenchymal-stem-cells-enhance-survival-under-hypoxia
#17
Bhawna Chandravanshi, Ramesh Ramchandra Bhonde
In the present study we focused on the improvisation of islet survival in hypoxia.The Islet like cell aggregates (ICAs) derived from wharton's jelly mesenchymal stem cells (WJ MSC) were cultured with and without WJ MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin,Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitated highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28097390/a-role-of-plc-pkc-dependent-pathway-in-glp-1-stimulated-insulin-secretion
#18
REVIEW
Makoto Shigeto, Chae Young Cha, Patrik Rorsman, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) is an endogenous glucose-lowering hormone and GLP-1 receptor agonists are currently being used as antidiabetic drugs clinically. The canonical signalling pathway (including cAMP, Epac2, protein kinase A (PKA) and KATP channels) is almost universally accepted as the main mechanism of GLP-1-stimulated insulin secretion. This belief is based on in vitro studies that used nanomolar (1-100 nM) concentrations of GLP-1. Recently, it was found that the physiological concentrations (1-10 pM) of GLP-1 also stimulate insulin secretion from isolated islets, induce membrane depolarization and increase of intracellular [Ca(2+)] in isolated β cells/pancreatic islets...
January 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28097011/a-selective-gpr40-ffar1-agonist-ly2881835-provides-immediate-and-durable-glucose-control-in-rodent-models-of-type-2-diabetes
#19
Yanyun Chen, Min Song, Jonathan P Riley, Charlie C Hu, Xianbu Peng, Donalyn Scheuner, Krister Bokvist, Pranab Maiti, Steven D Kahl, Chahrzad Montrose-Rafizadeh, Chafiq Hamdouchi, Anne Reifel Miller
LY2881835 is a selective, potent, and efficacious GPR40 agonist. The objective of the studies described here was to examine the pharmacological properties of LY2881835 in preclinical models of T2D. Significant increases in insulin secretion were detected when LY2881835 was tested in primary islets from WT mice but not in islets from GPR40 KO mice. Furthermore, LY2881835 potentiated glucose stimulated insulin secretion in normal lean mice. Acute administration of LY2881835 lowered glucose during OGTTs in WT mice but not in GPR40 KO mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28096222/first-infant-formula-type-and-risk-of-islet-autoimmunity-in-the-environmental-determinants-of-diabetes-in-the-young-teddy-study
#20
Sandra Hummel, Andreas Beyerlein, Roy Tamura, Ulla Uusitalo, Carin Andrén Aronsson, Jimin Yang, Anne Riikonen, Åke Lernmark, Marian J Rewers, William A Hagopian, Jin-Xiong She, Olli G Simell, Jorma Toppari, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Suvi M Virtanen, Jill M Norris
OBJECTIVE: Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow's milk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort. RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively monitors 8,676 children at increased genetic risk for T1D...
January 17, 2017: Diabetes Care
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