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https://www.readbyqxmd.com/read/29117231/human-pancreatic-islet-derived-extracellular-vesicles-modulate-insulin-expression-in-3d-differentiating-ipsc-clusters
#1
Diana Ribeiro, Eva-Marie Andersson, Nikki Heath, Anette Persson-Kry, Richard Collins, Ryan Hicks, Niek Dekker, Anna Forslöw
It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs) were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC) clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#2
REVIEW
Yaxi Zhu, Qian Liu, Zhiguang Zhou, Yasuhiro Ikeda
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells...
November 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29070792/mir-204-is-associated-with-an-endocrine-phenotype-in-human-pancreatic-islets-but-does-not-regulate-the-insulin-mrna-through-mafa
#3
Ilaria Marzinotto, Silvia Pellegrini, Cristina Brigatti, Rita Nano, Raffaella Melzi, Alessia Mercalli, Daniela Liberati, Valeria Sordi, Maurizio Ferrari, Massimo Falconi, Claudio Doglioni, Philippe Ravassard, Lorenzo Piemonti, Vito Lampasona
miR-204 has been proposed to modulate insulin expression in human pancreatic islets by regulating the expression of the MAFA transcript, and in turn insulin transcription. We investigated miR-204 expression in pancreatic endocrine tumors (PET), a panel of human tissues, tissues derived from pancreatic islet purification, and in induced pluripotent stem cells (iPSCs) differentiated towards a pancreatic endocrine phenotype by quantitative real time RT-PCR or droplet digital PCR (ddPCR). In addition, we evaluated the effect of miR-204 up- or down-regulation in purified human islets and in the EndoC-βH1 cell line, as an experimental model of human pancreatic β cells...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29029025/insulin-deficient-mouse-%C3%AE-cells-do-not-fully-mature-but-can-be-remedied-through-insulin-replacement-by-islet-transplantation
#4
Adam Ramzy, Majid Mojibian, Timothy J Kieffer
Insulin receptor insufficiency in β-cells leads to impaired insulin secretion and reduced β-cell hyperplasia in response to hyperglycemia. Selective insulin receptor deficiency in β-cells in later embryological development may lead to compensatory β-cell hyperplasia. Though these findings suggest insulin signaling on the β-cell is important for β-cell function, they are confounded by loss of signaling by the IGFs through the insulin receptor. To determine if insulin itself is necessary for β-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both non-allelic insulin genes (Ins1-/-Ins2-/-)...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28980863/addition-of-exogenous-sodium-palmitate-increases-the-iapp-insulin-mrna-ratio-via-gpr40-in-human-endoc-%C3%AE-h1-cells
#5
Camilla Krizhanovskii, Rikard G Fred, Marie E Oskarsson, Gunilla T Westermark, Nils Welsh
BACKGROUND: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells. METHODS: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms...
August 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/28970780/mulberry-branch-bark-powder-significantly-improves-hyperglycemia-and-regulates-insulin-secretion-in-type-ii-diabetic-mice
#6
Xiao-Lu Yin, Hua-Yu Liu, Yu-Qing Zhang
This experiment, based on the previous study on R. mori, introduces whole mulberry branch powder into the diet to treat diabetic mice. Mulberry branch bark powder (MBBP) was administered orally to streptozotocin (STZ)-induced type II diabetic (T2D) mice to investigate hypoglycemic effects. After a 4-week period of diet consumption containing 5%, 10% and 20% MBBP, the fasting blood glucose, body weight and the related western blotting were measured, pathologic and immunohistochemical were observed. The 20% MBBP group showed a significant reduction in hyperglycemia and hyperinsulinemia; fasting blood glucose and insulin decreased from 25...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#7
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933784/inhibition-of-the-deubiquitinase-usp5-leads-to-c-maf-protein-degradation-and-myeloma-cell-apoptosis
#8
Siyu Wang, Jiaxiang Juan, Zubin Zhang, Yanyun Du, Yujia Xu, Jiefei Tong, Biyin Cao, Michael F Moran, Yuanying Zeng, Xinliang Mao
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28931519/beta-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#9
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
September 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28924486/expression-of-transcription-factors-in-men1-associated-pancreatic-neuroendocrine-tumors
#10
Yasutaka Takeda, Yukihiro Fujita, Kentaro Sakai, Tomoe Abe, Tomonobu Nakamura, Tsuyoshi Yanagimachi, Hidemitsu Sakagami, Jun Honjo, Atsuko Abiko, Yuichi Makino, Masakazu Haneda
MEN1-associated pancreatic neuroendocrine tumors (pNETs) may potentially express distinct hormones, but the mechanism has not been elucidated. Transcription factors such as MafA and Pdx1 have been identified to lead to beta cell differentiation, while Arx and Brn4 to alpha cell differentiation in developing pancreas. We hypothesized those transcription factors are important to produce specific hormones in pNETs, similarly to developing pancreas, and examined the expression of transcription factors in a case of MEN1 who showed immunohistological coexistence of several hormone-producing pNETs including insulinoma...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28918929/vitamin-d-receptor-targeted-treatment-to-prevent-pathological-dedifferentiation-of-pancreatic-%C3%AE-cells-under-hyperglycaemic-stress
#11
A Neelankal John, Z Iqbal, S Colley, G Morahan, M Makishima, F-X Jiang
Dedifferentiation has been identified as one of the causes of β-cell failure resulting in type 2 diabetes (T2D). This study tested whether increasing vitamin D receptor (VDR) expression prevents dedifferentiation of β cells in a high-glucose state in vitro. Culturing a mouse insulinoma cell line (MIN6) in a high-glucose environment decreased VDR expression. However, increased VDR following vitamin D3 (VD3) treatment improved insulin release of early-passage MIN6 and insulin index of db/- (heterozygous) islets to levels seen in normal functional islets...
September 11, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28918023/repression-of-coup-tfi-improves-bone-marrow-derived-mesenchymal-stem-cell-differentiation-into-insulin-producing-cells
#12
Tao Zhang, Xiao-Hang Li, Dian-Bao Zhang, Xiao-Yu Liu, Feng Zhao, Xue-Wen Lin, Rui Wang, Hong-Xin Lang, Xi-Ning Pang
Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI)...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28882998/transplantation-of-ips-derived-tumor-cells-with-a-homozygous-mhc-haplotype-induces-grp94-antibody-production-in-mhc-matched-macaques
#13
Hirohito Ishigaki, Toshinaga Maeda, Hirokazu Inoue, Tsuyoshi Akagi, Takako Sasamura, Hideaki Ishida, Toshiro Inubushi, Junko Okahara, Takashi Shiina, Misako Nakayama, Yasushi Itoh, Kazumasa Ogasawara
Immune surveillance is a critical component of the antitumor response in vivo, yet the specific components of the immune system involved in this regulatory response remain unclear. In this study, we demonstrate that autoantibodies can mitigate tumor growth in vitro and in vivo We generated two cancer cell lines, embryonal carcinoma and glioblastoma cell lines, from monkey-induced pluripotent stem cells (iPSC) carrying a homozygous haplotype of major histocompatibility complex (MHC, Mafa in Macaca fascicularis)...
September 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28873332/use-of-rgd-functionalized-sandwich-cultures-to-promote-redifferentiation-of-human-pancreatic-beta-cells-after-in-vitro-expansion
#14
Caterina Aloy-Reverté, José L Moreno-Amador, Montserrat Nacher, Eduard Montanya, Carlos E Semino
Islet transplantation has provided proof of concept that cell therapy can restore normoglycemia in patients with diabetes. However, limited availability of islet tissue severely restricts the clinical use of the treatment. Thus, there is an urgent need to develop new strategies to generate an abundant source of insulin-producing cells that could be used to treat diabetes. A potential approach is the in vitro expansion of pancreatic beta cells obtained from cadaveric organ donors. However, when human beta cells are expanded in vitro, they dedifferentiate and lose the expression of insulin, probably as a consequence of pancreatic islet dissociation into single cells...
August 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28817206/loureirin-b-promotes-insulin-secretion-through-inhibition-of-katp-channel-and-influx-of-intracellular-calcium
#15
Yijie Sha, Yuelin Zhang, Jing Cao, Kai Qian, Bing Niu, Qin Chen
The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For searching the promotion of insulin secretion with the treatment of loureirin B, experiments were employed based on cell experiments and computational methods. Firstly, promotion of insulin secretion was dependent on extracellular glucose concentration. At the genetic level, loureirin B enhanced the relative mRNA level of Pdx-1 and MafA...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28813430/reprogramming-human-gallbladder-cells-into-insulin-producing-%C3%AE-like-cells
#16
Feorillo Galivo, Eric Benedetti, Yuhan Wang, Carl Pelz, Jonathan Schug, Klaus H Kaestner, Markus Grompe
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28765173/a2a-adenosine-receptors-control-pancreatic-dysfunction-in-high-fat-diet-induced-obesity
#17
Balázs Csóka, Gábor Törő, Joana Vindeirinho, Zoltán V Varga, Balázs Koscsó, Zoltán H Németh, Endre Kókai, Luca Antonioli, Mara Suleiman, Piero Marchetti, Karolina Cseri, Ádám Deák, László Virág, Pál Pacher, Péter Bai, György Haskó
Adenosine, a key extracellular signaling mediator, regulates several aspects of metabolism by activating 4 G protein-coupled receptors, the A1, A2A, A2B, and A3 adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)-induced metabolic derangements is unknown. To evaluate the role of A2AARs in regulating glucose and insulin homeostasis in obesity, we fed A2AAR knockout (KO) and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We found that genetic deletion of A2AARs caused impaired glucose tolerance in mice fed an HFD...
August 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28739109/generation-of-glucose-sensitive-insulin-secreting-beta-like-cells-from-human-embryonic-stem-cells-by-incorporating-a-synthetic-lineage-control-network
#18
Pratik Saxena, Daniel Bojar, Henryk Zulewski, Martin Fussenegger
We previously reported novel technology to differentiate induced pluripotent stem cells (IPSCs) into glucose-sensitive insulin-secreting beta-like cells by engineering a synthetic lineage-control network regulated by the licensed food additive vanillic acid. This genetic network was able to program intricate expression dynamics of the key transcription factors Ngn3 (neurogenin 3, OFF-ON-OFF), Pdx1 (pancreatic and duodenal homeobox 1, ON-OFF-ON) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A, OFF-ON) to guide the differentiation of IPSC-derived pancreatic progenitor cells to beta-like cells...
July 22, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#19
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28647274/sonic-hedgehog-pathway-suppression-and-reactivation-accelerates-differentiation-of-rat-adipose-derived-mesenchymal-stromal-cells-toward-insulin-producing-cells
#20
Dian Dayer, Mahmoud Hashemi Tabar, Eskandar Moghimipour, Mohammad Reza Tabandeh, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
BACKGROUND AIMS: Sonic hedgehog (Shh) is an intercellular signaling molecule that regulates pancreas development in mammals. Manipulation of Shh signaling pathway can be used as reliable approach to improve the generation of functional insulin-producing cells (IPCs) from mesenchymal stromal cells (MSCs). METHODS: In the present study, a novel differentiation protocol was used to produce IPCs from adipose tissue-derived MSCs (ATDMSCs) based on sequential inhibition and reactivation of Shh pathway...
June 21, 2017: Cytotherapy
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