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https://www.readbyqxmd.com/read/28448818/pegylated-bilirubin-nanoparticle-as-an-anti-oxidative-and-anti-inflammatory-demulcent-in-pancreatic-islet-xenotransplantation
#1
Min Jun Kim, Yonghyun Lee, Sangyong Jon, Dong Yun Lee
Transplanted islets suffer hypoxic stress, which leads to nonspecific inflammation. This is the major cause of islet graft failure during the early stage of intrahepatic islet transplantation. Although bilirubin has shown potent anti-oxidative and anti-inflammatory functions, its clinical applications have been limited due to its insolubility and short half-life. To overcome this problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28448538/combined-lipidomic-and-proteomic-analysis-of-isolated-human-islets-exposed-to-palmitate-reveals-time-dependent-changes-in-insulin-secretion-and-lipid-metabolism
#2
Kirsten Roomp, Hjalti Kristinsson, Domitille Schvartz, Kumari Ubhayasekera, Ernest Sargsyan, Levon Manukyan, Azazul Chowdhury, Hannes Manell, Venkata Satagopam, Karlfried Groebe, Reinhard Schneider, Jonas Bergquist, Jean-Charles Sanchez, Peter Bergsten
Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/ or confirm reported mechanisms of lipotoxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28447752/islet-1-induces-the-differentiation-of-mesenchymal-stem-cells-into-cardiomyocyte-like-cells-through-the-regulation-of-gcn5-and-dnmt-1
#3
Qin Yi, Hao Xu, Ke Yang, Yue Wang, Bin Tan, Jie Tian, Jing Zhu
Previous studies from this group demonstrated that insulin gene enhancer binding protein ISL-1 (Islet-1) specifically induces the differentiation of mesenchymal stem cells (MSCs) into cardiomyocyte‑like cells through histone acetylation. However, the underlying mechanisms remain unclear. In the present study, the role of the histone acetylation and DNA methylation on the regulatory mechanism of the Islet‑1 was further investigated by methylation‑specific polymerase chain reaction (PCR), chromatin immunoprecipitation quantitative PCR and western blot analysis...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28445528/baicalein-protects-rat-insulinoma-ins-1-cells-from-palmitate-induced-lipotoxicity-by-inducing-ho-1
#4
Hyun Jeong Kwak, Dongki Yang, Yongha Hwang, Hee-Sook Jun, Hyae Gyeong Cheon
OBJECTIVE: β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1...
2017: PloS One
https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#5
Nizar I Mourad, Claire Crossan, Victoria Cruikshank, Linda Scobie, Pierre Gianello
BACKGROUND: Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression levels can vary considerably between individuals and within different tissues of a single animal. In general, expression levels have been found to be particularly low in the pancreas compared to other porcine tissues suggesting a reduced risk associated with the use of this tissue...
April 26, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28443133/analysis-of-purified-pancreatic-islet-beta-and-alpha-cell-transcriptomes-reveals-11%C3%AE-hydroxysteroid-dehydrogenase-hsd11b1-as-a-novel-disallowed-gene
#6
Timothy J Pullen, Mark O Huising, Guy A Rutter
We and others have previously identified a group of genes, dubbed "disallowed," whose expression is markedly lower in pancreatic islets than in other mammalian cell types. Forced mis-expression of several members of this family leads to defective insulin secretion, demonstrating the likely importance of disallowance for normal beta cell function. Up to now, transcriptomic comparisons have been based solely on data from whole islets. This raises the possibilities that (a) there may be important differences in the degree of disallowance of family members between beta and other either neuroendocrine cells; (b) beta (or alpha) cell disallowed genes may have gone undetected...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28442507/protein-kinase-stk25-aggravates-the-severity-of-non-alcoholic-fatty-pancreas-disease-in-mice
#7
Esther Nunez Duran, Belen Chanclon, Silva Sütt, Joana Real, Hanns-Ulrich Marschall, Ingrid Wernstedt-Asterholm, Emelie Cansby, Margit Mahlapuu
Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice...
April 25, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28442472/functional-and-metabolomic-consequences-of-atp-dependent-potassium-channel-inactivation-in-human-islets
#8
Changhong Li, Amanda M Ackermann, Kara E Boodhansingh, Tricia R Bhatti, Chengyang Liu, Jonathan Schug, Nicolai Doliba, Bing Han, Karen E Cosgrove, Indraneel Banerjee, Franz M Matschinsky, Itzhak Nissim, Klaus H Kaestner, Ali Naji, N Scott Adzick, Mark J Dunne, Charles A Stanley, Diva D De León
Loss-of-function mutations of β-cell KATP channels cause the most severe form of congenital hyperinsulinism (KATPHI). KATPHI is characterized by fasting and protein-induced hypoglycemia that is unresponsive to medical therapy. For a better understanding of the pathophysiology of KATPHI, we examined cytosolic calcium, insulin secretion, oxygen consumption, and [U-(13)C]glucose metabolism in islets isolated from the pancreases of children with KATPHI who required pancreatectomy. Basal cytosolic calcium ([Ca(2+)] i ) and insulin secretion were higher in KATPHI islets compared to controls...
April 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28441528/phosphorylation-of-neurog3-links-endocrine-differentiation-to-the-cell-cycle-in-pancreatic-progenitors
#9
Nicole A J Krentz, Dennis van Hoof, Zhongmei Li, Akie Watanabe, Mei Tang, Cuilan Nian, Michael S German, Francis C Lynn
During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28439640/the-elusive-role-of-b-lymphocytes-and-islet-autoantibodies-in-human-type-1-diabetes
#10
EDITORIAL
Stef J Bloem, Bart O Roep
The role of B lymphocytes in the pathogenesis of type 1 diabetes in humans is not entirely evident. These cells are presumed to be important, but this assumption is largely based on animal models of autoimmune diabetes, where compelling evidence for the contribution of both B lymphocytes and insulin-specific autoantibodies to this disease is in place. For humans, this is much less the case; the exact way in which B lymphocytes and/or autoantibodies may contribute to type 1 diabetes is not yet known but the possibilities include a pathogenic function ('fire'), or they may represent a surrogate of loss of immune tolerance to beta cells ('smoke') or, indeed, they could be a marker of an attempt at immune regulation ('ice water')...
April 24, 2017: Diabetologia
https://www.readbyqxmd.com/read/28439456/metformin-ameliorates-insulitis-in-stz-induced-diabetic-mice
#11
Xue Han, Yu-Long Tao, Ya-Ping Deng, Jia-Wen Yu, Jian Cai, Guo-Fei Ren, Yuan-Nan Sun, Guo-Jun Jiang
BACKGROUND & AIMS: Metformin is currently the most widely used first-line hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there is increasingly interest in the potential anti-inflammatory action of this drug. In the present study, we investigated the actions of metformin on experimental insulitis using STZ-induced diabetic mice. METHODS: Mice with acute diabetes induced by STZ were administered metformin by gavage. Changes of blood glucose and body weight, and the daily amount of food and water intake were measured...
2017: PeerJ
https://www.readbyqxmd.com/read/28439257/high-resolution-recording-of-the-circadian-oscillator-in-primary-mouse-%C3%AE-and-%C3%AE-cell-culture
#12
Volodymyr Petrenko, Yvan Gosmain, Charna Dibner
Circadian clocks have been developed in evolution as an anticipatory mechanism allowing for adaptation to the constantly changing light environment due to rotation of the Earth. This mechanism is functional in all light-sensitive organisms. There is a considerable body of evidence on the tight connection between the circadian clock and most aspects of physiology and metabolism. Clocks, operative in the pancreatic islets, have caught particular attention in the last years due to recent reports on their critical roles in regulation of insulin secretion and etiology of type 2 diabetes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28438776/the-immunoproteasome-is-induced-by-cytokines-and-regulates-apoptosis-in-human-islets
#13
Morten Lundh, Marco Bugliani, Tina Dahlby, Danny Hung-Chieh Chou, Bridget Wagner, Seyed Mojtaba Ghiasi, Vincenzo De Tata, Zhifei Chen, Marianne Nissen Lund, Michael J Davies, Piero Marchetti, Thomas Mandrup-Poulsen
In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. INS-1, INS-1E and human islets were exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules. Gene expression was assessed by microarray or quantitative PCR. Proteasome activities were analyzed using luminescent assays. Protein oxidation, Western blotting and electron microscopy were used to examine mechanisms underlying cytokine-induced apoptosis...
April 24, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28438671/alkaline-ph-induces-irr-mediated-phosphorylation-of-irs-1-and-actin-cytoskeleton-remodeling-in-a-pancreatic-beta-cell-line
#14
Igor E Deyev, Nadezhda V Popova, Oxana V Serova, Svetlana V Zhenilo, Marì Regoli, Eugenio Bertelli, Alexander G Petrenko
Secretion of mildly alkaline (pH 8.0-8.5) juice to intestines is one of the key functions of the pancreas. Recent reports indicate that the pancreatic duct system containing the alkaline juice may adjoin the endocrine cells of pancreatic islets. We have previously identified the insulin receptor-related receptor (IRR) that is expressed in islets as a sensor of mildly alkaline extracellular media. In this study, we show that those islet cells that are in contact with the excretory ducts are also IRR-expressing cells...
April 21, 2017: Biochimie
https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#15
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436697/liver-track-embolization-after-islet-cell-transplant-comparison-of-two-techniques
#16
Ron C Gaba, Kenji R Kobayashi, James T Bui, R Peter Lokken, Andrew J Lipnik, Charles E Ray, Jose Oberholzer
OBJECTIVE: The purpose of this study was to compare the efficacy and safety of microfibrillar collagen paste with those of gelatin sponge for liver track embolization after islet cell transplants. MATERIALS AND METHODS: In a single-institution, retrospective study, 37 patients underwent 66 islet cell transplants from January 2005 through October 2015. Transplants were performed with 6-French transhepatic access, systemic anticoagulation, pretransplant and posttransplant portal venous pressure measurement, and image-guided liver track embolization with gelatin sponge (2005-2011) or microfibrillar collagen paste (2012-2015)...
May 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28436095/berberine-alleviates-oxidative-stress-in-islets-of-diabetic-mice-by-inhibiting-mir-106b-expression-and-up-regulating-sirt1
#17
Dong-Liang Chen, Ke-Ya Yang
BACKGROUND: Mounting studies have indicated the role of berberine, SIRT1 and oxidative stress in diabetes, respectively. However, few studies have demonstrated their correlation and regulation function in diabetes. Therefore, the protective effect of berberine in diabetic and the underlying core mechanism were investigated in the current study. METHODS: Diabetic mice model in vivo were established. Mouse pancreatic beta-cell line NIT-1 cells were treated with 30 mM high glucose to induce diabetic condition in vitro...
April 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28435063/regulation-of-nampt-expression-by-transcriptional-coactivator-ncoa6-in-pancreatic-%C3%AE-cells
#18
Jin Yoon, Kyung Jin Lee, Gyun Sik Oh, Geun Hyang Kim, Seung-Whan Kim
Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator and crucial for insulin secretion and glucose metabolism in pancreatic β-cells. However, the regulatory mechanism of β-cell function by NCOA6 is largely unknown. In this study, we found that the transcript levels of nicotinamide phosphoribosyltransferase (Nampt) were decreased in islets of NCOA6(+/-) mice compared with NCOA6(+/+) mice. Moreover, NCOA6 overexpression increased the levels of Nampt transcripts in the mouse pancreatic β-cell line NIT-1...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28435021/the-mtorc2-pkc-pathway-sustains-compensatory-insulin-secretion-of-pancreatic-%C3%AE-cells-in-response-to-metabolic-stress
#19
Yun Xie, Canqi Cui, Aifang Nie, Yan Wang, Qicheng Ni, Yun Liu, Qinglei Yin, Hongli Zhang, Yong Li, Qidi Wang, Yanyun Gu, Guang Ning
BACKGROUND: Compensation of the pancreatic β cell functional mass in response to metabolic stress is key to the pathogenesis of Type 2 Diabetes. The mTORC2 pathway governs fuel metabolism and β cell functional mass. It is unknown whether mTORC2 is required for regulating metabolic stress-induced β cell compensation. METHODS: We challenged four-week-old β-cell-specific Rictor (a key component of mTORC2)-knockout mice with a high fat diet (HFD) for 4weeks and measured metabolic and pancreatic morphological parameters...
April 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28433740/xenotransplantation-of-layer-by-layer-encapsulated-non-human-primate-islets-with-a-specified-immunosuppressive-drug-protocol
#20
Muhammad R Haque, Jiwoong Kim, Hyojun Park, Han Sin Lee, Kyo Won Lee, Taslim A Al-Hilal, Jee-Heon Jeong, Cheol-Hee Ahn, Doo Sung Lee, Sung Joo Kim, Youngro Byun
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with human...
April 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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