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Pdx1

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https://www.readbyqxmd.com/read/28095440/comprehensive-maturity-onset-diabetes-of-the-young-mody-gene-screening-in-pregnant-women-with-diabetes-in-india
#1
Mahesh Doddabelavangala Mruthyunjaya, Aaron Chapla, Asha Hesarghatta Shyamasunder, Deny Varghese, Manika Varshney, Johan Paul, Mercy Inbakumari, Flory Christina, Ron Thomas Varghese, Kurien Anil Kuruvilla, Thomas V Paul, Ruby Jose, Annie Regi, Jessie Lionel, L Jeyaseelan, Jiji Mathew, Nihal Thomas
Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes...
2017: PloS One
https://www.readbyqxmd.com/read/28092359/lysine-relay-mechanism-coordinates-intermediate-transfer-in-vitamin-b6-biosynthesis
#2
Matthew J Rodrigues, Volker Windeisen, Yang Zhang, Gabriela Guédez, Stefan Weber, Marco Strohmeier, Jeremiah W Hanes, Antoine Royant, Gwyndaf Evans, Irmgard Sinning, Steven E Ealick, Tadhg P Begley, Ivo Tews
Substrate channeling has emerged as a common mechanism for enzymatic intermediate transfer. A conspicuous gap in knowledge concerns the use of covalent lysine imines in the transfer of carbonyl-group-containing intermediates, despite their wideuse in enzymatic catalysis. Here we show how imine chemistry operates in the transfer of covalent intermediates in pyridoxal 5'-phosphate biosynthesis by the Arabidopsis thaliana enzyme Pdx1. An initial ribose 5-phosphate lysine imine is converted to the chromophoric I320 intermediate, simultaneously bound to two lysine residues and partially vacating the active site, which creates space for glyceraldehyde 3-phosphate to bind...
January 16, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28087712/pdx1-dynamically-regulates-pancreatic-ductal-adenocarcinoma-initiation-and-maintenance
#3
Nilotpal Roy, Kenneth K Takeuchi, Jeanine M Ruggeri, Peter Bailey, David Chang, Joey Li, Laura Leonhardt, Sapna Puri, Megan T Hoffman, Shan Gao, Christopher J Halbrook, Yan Song, Mats Ljungman, Shivani Malik, Christopher V E Wright, David W Dawson, Andrew V Biankin, Matthias Hebrok, Howard C Crawford
Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for pancreatic and duodenal homeobox 1 (PDX1), a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of pancreatic intraepithelial neoplasia (PanIN)-derived PDA...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28059593/clinical-relevance-of-epigenetics-in-the-onset-and-management-of-type-2-diabetes-mellitus
#4
Linda Sommese, Alberto Zullo, Francesco Paolo Mancini, Rossella Fabbricini, Andrea Soricelli, Claudio Napoli
Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28052964/whole-genome-bisulfite-sequencing-of-human-pancreatic-islets-reveals-novel-differentially-methylated-regions-in-type-2-diabetes-pathogenesis
#5
Petr Volkov, Karl Bacos, Jones K Ofori, Jonathan Lou S Esguerra, Lena Eliasson, Tina Rönn, Charlotte Ling
Current knowledge about the role of epigenetics in type 2 diabetes (T2D) remains limited. Only a few studies have investigated DNA methylation of selected candidate genes or a very small fraction of genomic CpG sites in human pancreatic islets, the tissue of primary pathogenic importance for diabetes. Our aim was to characterize the whole-genome DNA methylation landscape in human pancreatic islets, to identify differentially methylated regions (DMRs) in diabetic islets, and to investigate the function of DMRs in islet biology...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28042537/the-convenience-of-single-homology-arm-donor-dna-and-crispr-cas9-nickase-for-targeted-insertion-of-long-dna-fragment
#6
Mohsen Basiri, Mehrdad Behmanesh, Yaser Tahamtani, Keynoosh Khalooghi, Azadeh Moradmand, Hossein Baharvand
OBJECTIVE: CRISPR/Cas9 technology provides a powerful tool for targeted modification of genomes. In this system, a donor DNA harboring two flanking homology arms is mostly used for targeted insertion of long exogenous DNA. Here, we introduced an alternative design for the donor DNA by incorporation of a single short homology arm into a circular plasmid. MATERIALS AND METHODS: In this experimental study, single homology arm donor was applied along with a single guide RNA (sgRNA) specific to the homology region, and either Cas9 or its mutant nickase variant (Cas9n)...
2017: Cell Journal
https://www.readbyqxmd.com/read/28041957/human-pancreatic-%C3%AE-cell-lncrnas-control-cell-specific-regulatory-networks
#7
Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M Y Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-Conte, Francois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis...
December 28, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28017717/preserving-expression-of-pdx1-improves-%C3%AE-cell-failure-in-diabetic-mice
#8
Yuichi Yamamoto, Takeshi Miyatsuka, Shugo Sasaki, Kazuyuki Miyashita, Fumiyo Kubo, Naoki Shimo, Satomi Takebe, Hirotaka Watada, Hideaki Kaneto, Taka-Aki Matsuoka, Iichiro Shimomura
Pdx1, a β-cell-specific transcription factor, has been shown to play a crucial role in maintaining β-cell function through transactivation of β-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against β-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in β cells (βPdx1) and crossed these mice with Ins2(Akita) diabetic mice...
December 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28017506/insulin-producing-cells-generation-by-overexpression-of-mir-375-in-adipose-derived-mesenchymal-stem-cells-from-diabetic-patients
#9
Mehran Piran, Seyed Ehsan Enderami, Mehrdad Piran, Hadis Soltani Sedeh, Ehsan Seyedjafari, Abdolreza Ardeshirylajimi
Diabetes Mellitus (DM) is a systematic disease, which happens because of destruction of islets of Langerhans in the pancreas and systematic resistance to insulin. The lack of donor for pancreas transplantation and risk of transplant rejection is the main challenge in the treatment of this disease. Stem cells are proper and sufficient source for creating insulin-producing cells (IPC). In this study adipose tissue was provided from diabetic patients operated for liposuction and then adipose derived stem cells (ADSCs) were isolated, characterized and then treated by lentiviruses containing miR-375, after 7, 14 and 21 days of induction, islet-like clusters (ILC) specific genes including insulin and PDX1 were evaluated by Real Time RT-PCR...
December 22, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28000178/quercetin-potentiates-transdifferentiation-of-bone-marrow-mesenchymal-stem-cells-into-the-beta-cells-in-vitro
#10
B Miladpour, M Rasti, A A Owji, Z Mostafavipour, Z Khoshdel, A Noorafshan, F Zal
PURPOSE: Type 1 diabetes is an autoimmune disease caused by the destruction of β-cells in the pancreas. Bone marrow mesenchymal stem cells are multipotent and easy accessible adult stem cells that may provide options in the treatment of type 1 diabetes. Injured pancreatic extract can promote the differentiation of rat bone marrow mesenchymal stem cells into β-cells. We aimed to observe the effect of quercetin in differentiation and insulin secretion in β-cells. METHODS: Bone marrow mesenchymal stem cells were obtained from the tibiae of rats...
December 20, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27998294/directed-differentiation-of-human-ipsc-into-insulin-producing-cells-is-improved-by-induced-expression-of-pdx1-and-nkx6-1-factors-in-ipc-progenitors
#11
Maciej P Walczak, Anna M Drozd, Ewelina Stoczynska-Fidelus, Piotr Rieske, Dawid P Grzela
BACKGROUND: Induced pluripotent stem cells (iPSC) possess an enormous potential as both, scientific and therapeutic tools. Their application in the regenerative medicine provides new treatment opportunities for numerous diseases, including type 1 diabetes. In this work we aimed to derive insulin producing cells (IPC) from iPS cells established in defined conditions. METHODS: We optimized iPSC generation protocol and created pluripotent cell lines with stably integrated PDX1 and NKX6...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27993987/the-mammal-specific-pdx1-area-ii-enhancer-has-multiple-essential-functions-in-early-endocrine-cell-specification-and-postnatal-%C3%AE-cell-maturation
#12
Yu-Ping Yang, Mark A Magnuson, Roland Stein, Christopher V E Wright
The transcription factor Pdx1 is required for multiple aspects of pancreatic organogenesis. It remains unclear to what extent Pdx1 expression and function depend upon trans-activation through 5' conserved cis-regulatory regions and, in particular, whether the mammal-specific Area II (-2139 to -1958 bp) affects minor or major aspects of organogenesis. We show that Area II is a primary effector of endocrine-selective transcription in epithelial multipotent cells, nascent endocrine progenitors, and differentiating and mature β cells in vivo Pdx1(ΔAREAII/-) mice exhibit a massive reduction in endocrine progenitor cells and progeny hormone-producing cells, indicating that Area II activity is fundamental to mounting an effective endocrine lineage-specification program within the multipotent cell population...
January 15, 2017: Development
https://www.readbyqxmd.com/read/27960594/development-of-islet-organoids-from-h9-human-embryonic-stem-cells-in-biomimetic-3d-scaffolds
#13
Weiwei Wang, Sha Jin, Kaiming Ye
Success in the differentiating human embryonic stem cells (hESCs) into insulin-secreting β cells raises new hopes for diabetes treatment. In this work, we demonstrated the feasibility of developing islet organoids from hESCs within biomimetic 3D scaffolds. We showed that such a 3D microenvironment is critical to the generation of pancreatic endoderm and endocrine from hESCs. The organoids formed consisted of pancreatic α, β, δ, and pancreatic polypeptide (PP) cells. A high level co-expression of PDX1, NKX6...
December 13, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27941872/er-stress-protein-agr2-precedes-and-is-involved-in-the-regulation-of-pancreatic-cancer-initiation
#14
L Dumartin, W Alrawashdeh, S M Trabulo, T P Radon, K Steiger, R M Feakins, M P di Magliano, C Heeschen, I Esposito, N R Lemoine, T Crnogorac-Jurcevic
The mechanisms of initiation of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. In the present study, we analysed the role of anterior gradient-2 (AGR2) in the earliest stages of pancreatic neoplasia. Immunohistochemical analysis of chronic pancreatitis (CP) and peritumoral areas in PDAC tissues showed that AGR2 was present in tubular complexes (TC) and early pancreatic intraepithelial neoplasia (PanINs). Moreover, AGR2 was also found in discrete subpopulations of non-transformed cells neighbouring these pre-neoplastic lesions...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27941246/lim-domain-binding-1-maintains-the-terminally-differentiated-state-of-pancreatic-%C3%AE-cells
#15
Benjamin N Ediger, Hee-Woong Lim, Christine Juliana, David N Groff, LaQueena T Williams, Giselle Dominguez, Jin-Hua Liu, Brandon L Taylor, Erik R Walp, Vasumathi Kameswaran, Juxiang Yang, Chengyang Liu, Chad S Hunter, Klaus H Kaestner, Ali Naji, Changhong Li, Maike Sander, Roland Stein, Lori Sussel, Kyoung-Jae Won, Catherine Lee May, Doris A Stoffers
The recognition of β cell dedifferentiation in type 2 diabetes raises the translational relevance of mechanisms that direct and maintain β cell identity. LIM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes promoter-enhancer looping, thereby directing fate assignment and maturation of progenitor populations. Many terminally differentiated endocrine cell types, however, remain enriched for LDB1, but its role is unknown. Here, we have demonstrated a requirement for LDB1 in maintaining the terminally differentiated status of pancreatic β cells...
January 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27925870/hydrogen-sulfide-enhances-pancreatic-%C3%AE-cell-differentiation-from-human-tooth-under-normal-and-glucotoxic-conditions
#16
Ioan Valentin Matei, Hisataka Ii, Ken Yaegaki
AIM: Glucotoxicity obstructs pancreatic differentiation from adult stem cells. The aim was to develop a novel protocol for differentiation of dental pulp stem cells (DPSCs) into pancreatic β cells and determine the effect of H2S on glucotoxicity. MATERIALS & METHODS: DPSCs were differentiated with media containing 5.5 or 25.0 mM glucose, exposed to 1 ng/ml H2S. Glucotoxicity, expression of β-cell markers, INS, PDX1 and GLUT2, and PI3K/AKT pathway were assessed...
December 7, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27909715/a-new-scaffold-containing-small-intestinal-submucosa-and-mesenchymal-stem-cells-improves-pancreatic-islet-function-and-survival-in%C3%A2-vitro-and-in%C3%A2-vivo
#17
Dan Wang, Xiaoming Ding, Wujun Xue, Jin Zheng, Xiaohui Tian, Yang Li, Xiaohong Wang, Huanjin Song, Hua Liu, Xiaohui Luo
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27899417/emerging-roles-of-glis3-in-neonatal-diabetes-type-1-and-type-2-diabetes
#18
Xianjie Wen, Yisheng Yang
GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid, and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism, and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations...
November 29, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27891681/incomplete-re-expression-of-neuroendocrine-progenitor-stem-cell-markers-is-a-key-feature-of-%C3%AE-cell-dedifferentiation
#19
Abraham Neelankal John, Grant Morahan, Fang-Xu Jiang
There is increasing evidence to suggest that type 2 diabetes mellitus (T2D), a pandemic metabolic disease, may be caused by β-cell dedifferentiation (βCD). However, there is currently no universal definition of βCD, and the underlying mechanism is poorly understood. We hypothesise that a high-glucose in-vitro environment mimics hyperglycaemia in vivo and that β cells grown in this milieu over a long period will undergo dedifferentiation. Herein, we report that the pancreatic β cell line MIN6 grown under a high-glucose condition did not undergo massive cell death but exhibited a glucose-stimulated insulin-secreting profile similar to that of immature β cells...
November 28, 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27889714/neonatal-diabetes-a-case-series
#20
Ramaswamy Ganesh, Natarajan Suresh, Thiruvengadam Vasanthi, K G Ravikumar
BACKGROUND: Neonatal Diabetes Mellitusis a rare disorder with an incidence of 1 in 2,60,000 live births. METHODS: Retrospective analysis of clinical and genetic profile of children admitted with neonatal diabetes mellitus in a tertiary care hospital in Chennai, India over 11 years. RESULTS: Ten children were diagnosed with neonatal diabetes of whom 9 had permanent neonatal diabetes mellitus. The age range at onset was from 3 days- 5 months...
November 5, 2016: Indian Pediatrics
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