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https://www.readbyqxmd.com/read/29317564/pdx1-gene-mutation-with-permanent-neonatal-diabetes-mellitus-with-annular-pancreas-duodenal-atresia-hypoplastic-gall-bladder-and-exocrine-pancreatic-insufficiency
#1
Abhishek Kulkarni, Varun K Sharma, Fazal Nabi
BACKGROUND: Neonatal diabetes mellitus is a rare condition. CASE CHARACTERISTICS: A small for gestational age male, presented with neonatal onset diabetes mellitus, duodenal atresia, annular pancreas and gall bladder hypoplasia. OBSERVATION: Observation: A novel homozygous mutation p.K163R (c.488A>G) in the PDX1 gene was found. Parents were heterozygous for the same. MESSAGE: This case highlights the importance of establishing the genetic diagnosis in all cases of neonatal diabetes mellitus...
December 15, 2017: Indian Pediatrics
https://www.readbyqxmd.com/read/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#2
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29304337/alpha-to-beta-cell-reprogramming-stepping-toward-a-new-treatment-for-diabetes
#3
Anna B Osipovich, Mark A Magnuson
Beta cell replacement strategies hold promise for permanently treating type 1 diabetes. In Cell Stem Cell, Xiao et al. (2018) restore pancreatic beta cell mass and normalize blood glucose in diabetic mice by reprogramming pancreatic alpha to beta cells using Pdx1- and Mafa-expressing adeno-associated virus infused into the pancreatic duct.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29298796/development-and-preclinical-validation-of-a-cysteine-knottin-peptide-targeting-integrin-%C3%AE-v%C3%AE-6-for-near-infrared-fluorescent-guided-surgery-in-pancreatic-cancer
#4
Willemieke Sfj Tummers, Richard H Kimura, Lotfi Abou-Elkacem, Alexander L Vahrmeijer, Rutger-Jan Swijnenburg, Juergen K Willmann, Sanjiv S Gambhir
PURPOSE: Intraoperative near-infrared fluorescence (NIRF) imaging could help stratification for the proper primary treatment for patients with pancreatic ductal adenocarcinoma (PDAC), and achieve complete resection since it allows visualization of cancer in real time. Integrin αvβ6, a target specific for PDAC, is present in >90% of patients, and is able to differentiate between pancreatitis and PDAC. A clinically translatable αvβ6-targeting NIRF agent was developed, based on a previously developed cysteine knottin peptide for PET imaging, R01-MG, and validated in preclinical mouse models...
January 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29289465/investigating-the-role-of-transcription-factors-of-pancreas-development-in-pancreatic-cancer
#5
REVIEW
Ahmad Abu Turab Naqvi, Gulam Mustafa Hasan, Md Imtaiyaz Hassan
Pancreatic cancer (PC) is the seventh most common cause of cancer-related deaths worldwide that kills more than 300,000 people every year. Prognosis of PC is very poor with a five-year survival rate about 5%. The most common and highly observed type of PC is pancreatic ductal adenocarcinoma (PDAC). It is preceded by the progression of precursor lesions such as Pancreatic Intraepithelial Neoplasia (PanIN), Intraductal Papillary Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). PanIN is the most common among these premalignant lesions...
December 24, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29249692/%C3%AE-2-adrenergic-neurotrophin-feedforward-loop-promotes-pancreatic-cancer
#6
Bernhard W Renz, Ryota Takahashi, Takayuki Tanaka, Marina Macchini, Yoku Hayakawa, Zahra Dantes, H Carlo Maurer, Xiaowei Chen, Zhengyu Jiang, C Benedikt Westphalen, Matthias Ilmer, Giovanni Valenti, Sarajo K Mohanta, Andreas J R Habenicht, Moritz Middelhoff, Timothy Chu, Karan Nagar, Yagnesh Tailor, Riccardo Casadei, Mariacristina Di Marco, Axel Kleespies, Richard A Friedman, Helen Remotti, Maximilian Reichert, Daniel L Worthley, Jens Neumann, Jens Werner, Alina C Iuga, Kenneth P Olive, Timothy C Wang
Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras+/G12D;Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras+/G12D;LSL-Trp53+/R172H;Pdx1-Cre (KPC) mice...
December 1, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29248441/kr%C3%A3-ppel-like-factor-5-increased-in-pancreatic-ductal-adenocarcinoma-promotes-proliferation-acinar-to-ductal-metaplasia-pancreatic-intraepithelial-neoplasia-and-tumor-growth-in-mice
#7
Ping He, Jong Won Yang, Vincent W Yang, Agnieszka B Bialkowska
BACKGROUND & AIMS: Activating mutations in KRAS are detected in most pancreatic ductal adenocarcinomas (PDACs). Expression of an activated form of KRAS (KrasG12D) in pancreata of mice is sufficient to induce formation of pancreatic intraepithelial neoplasia (PanINs)-a precursor of PDAC. Pancreatitis increases formation of PanINs in mice that express KrasG12D by promoting acinar to ductal metaplasia (ADM). We investigated the role of the transcription factor Krüppel-like factor 5 (KLF5) in ADM and KRAS-mediated formation of PanINs...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#8
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29235528/identification-of-newly-committed-pancreatic-cells-in-the-adult-mouse-pancreas
#9
Mairobys Socorro, Angela Criscimanna, Patricia Riva, Manuj Tandon, Krishna Prasadan, Ping Guo, Abhinav Humar, Sohail Z Husain, Steven D Leach, George K Gittes, Farzad Esni
Multipotent epithelial cells with high Aldehyde dehydrogenase activity have been previously reported to exist in the adult pancreas. However, whether they represent true progenitor cells remains controversial. In this study, we isolated and characterized cells with ALDH activity in the adult mouse or human pancreas during physiological conditions or injury. We found that cells with ALDH activity are abundant in the mouse pancreas during early postnatal growth, pregnancy, and in mouse models of pancreatitis and type 1 diabetes (T1D)...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234093/crispr-cas9-microinjection-in-oocytes-disables-pancreas-development-in-sheep
#10
Marcela Vilarino, Sheikh Tamir Rashid, Fabian Patrik Suchy, Bret Roberts McNabb, Talitha van der Meulen, Eli J Fine, Syed Ahsan, Nurlybek Mursaliyev, Vittorio Sebastiano, Santiago Sain Diab, Mark O Huising, Hiromitsu Nakauchi, Pablo J Ross
One of the ultimate goals of regenerative medicine is the generation of patient-specific organs from pluripotent stem cells (PSCs). Sheep are potential hosts for growing human organs through the technique of blastocyst complementation. We report here the creation of pancreatogenesis-disabled sheep by oocyte microinjection of CRISPR/Cas9 targeting PDX1, a critical gene for pancreas development. We compared the efficiency of target mutations after microinjecting the CRISPR/Cas9 system in metaphase II (MII) oocytes and zygote stage embryos...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29232661/downregulation-of-long-noncoding-rna-gas5-affects-cell-cycle-and-insulin-secretion-in-mouse-pancreatic-%C3%AE-cells
#11
Feiyan Jin, Ning Wang, Yanan Zhu, Lianghui You, Lintao Wang, Wei De, Wei Tang
BACKGROUND: Evidence shows that long non-coding RNAs (lncRNAs) are involved in individual development, cell differentiation, cell cycle processes and other important life processes and are closely related to major human diseases, including diabetes. Recent studies have reported that lncRNAs are involved in β cell functions and that lncRNA Gas5 levels decreased in T2DM patients' serum. The purpose of this study was to clarify the role of lncRNA Gas5 in mouse β cell functions in vitro and in vivo...
October 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29220426/isl1%C3%AE-over-expression-with-key-%C3%AE-cell-transcription-factors-enhances-glucose-responsive-hepatic-insulin-production-and-secretion
#12
Yunshin Jung, Ruyi Zhou, Toshiki Kato, Jeffrey K Usui, Masafumi Muratani, Hisashi Oishi, Margarete M S Heck, Satoru Takahashi
Adenoviral gene transfer of key β cell developmental regulators including Pdx1, Neurod1 and Mafa (PDA) has been reported to generate insulin-producing cells in liver. However, PDA insulin secretion is transient and glucose unresponsive. Here, we report that an additional β cell developmental regulator, insulin gene enhancer binding protein splicing variant (Isl1β), improved insulin production and glucose-responsive secretion in PDA mouse. Microarray gene expression analysis suggested that adenoviral PDA transfer required an additional element for mature β cell generation, such as Isl1 and Elf3 in liver...
December 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/29210770/in-vitro-generation-of-glucose-responsive-insulin-secreting-cells-from-pancreatic-and-duodenal-homeobox-1-overexpressing-human-induced-pluripotent-stem-cell-derived-from-diabetic-patient
#13
Bahareh Rajaei, Mehdi Shamsara, Mohammad Hossein Sanati
Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription factor family, is a key transcription factor for pancreas development and mature β-cell function. In this study, induced overexpression of PDX1 resulted in producing susceptible cells for pancreatic differentiation and was well beneficial to enhance β-cell production, maturation, function, and survival. Induced PDX1 overexpression in harmony with a set of signaling molecules involves in guiding the signaling pathways toward pancreas development, leaded to high-efficient in vitro generation of ectopic insulin-producing cells (IPCs) with the effectively reduced number of polyhormonal cells and increased number of INS single-positive cells...
November 27, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/29192771/phenolic-substances-from-ocimum-species-enhance-glucose-stimulated-insulin-secretion-and-modulate-the-expression-of-key-insulin-regulatory-genes-in-mice-pancreatic-islets
#14
Livia Marques Casanova, Wenqian Gu, Sônia Soares Costa, Per Bendix Jeppesen
Ocimum gratissimum and Ocimum basilicum are plants ethnopharmacologically used to treat diabetes mellitus, a life-threatening disease that affects millions of people worldwide. In order to further understand their antidiabetic potential, which has been previously demonstrated in animal models, we aimed to investigate the acute and chronic effects of major phenolic substances from both plants on insulin secretion and gene expression in pancreatic islets isolated from NMRI mice. Insulin secretion was measured after acute (1 h) and long-term (72 h) incubation of islets with one of four cinnamic acid derivatives (caftaric, caffeic, chicoric, and rosmarinic acids) or a C-glucosylated flavonoid (vicenin-2)...
December 1, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29186652/combination-of-obestatin-and-bone-marrow-mesenchymal-stem-cells-prevents-aggravation-of-endocrine-pancreatic-damage-in-type-ii-diabetic-rats
#15
Noha I Hussien, Nesrine Ebrahim, Ola M Mohammed, Dina Sabry
One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin improves the generation of functional β cells/islet-like cell clusters in vitro, suggesting implications for cell-based replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs and obestatin on an experimental model of type II diabetes mellitus (T2DM)...
November 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29185012/systems-biology-of-the-imidia-biobank-from-organ-donors-and-pancreatectomised-patients-defines-a-novel-transcriptomic-signature-of-islets-from-individuals-with-type-2-diabetes
#16
Michele Solimena, Anke M Schulte, Lorella Marselli, Florian Ehehalt, Daniela Richter, Manuela Kleeberg, Hassan Mziaut, Klaus-Peter Knoch, Julia Parnis, Marco Bugliani, Afshan Siddiq, Anne Jörns, Frédéric Burdet, Robin Liechti, Mara Suleiman, Daniel Margerie, Farooq Syed, Marius Distler, Robert Grützmann, Enrico Petretto, Aida Moreno-Moral, Carolin Wegbrod, Anke Sönmez, Katja Pfriem, Anne Friedrich, Jörn Meinel, Claes B Wollheim, Gustavo B Baretton, Raphael Scharfmann, Everson Nogoceke, Ezio Bonifacio, Dorothée Sturm, Birgit Meyer-Puttlitz, Ugo Boggi, Hans-Detlev Saeger, Franco Filipponi, Mathias Lesche, Paolo Meda, Andreas Dahl, Leonore Wigger, Ioannis Xenarios, Mario Falchi, Bernard Thorens, Jürgen Weitz, Krister Bokvist, Sigurd Lenzen, Guy A Rutter, Philippe Froguel, Manon von Bülow, Mark Ibberson, Piero Marchetti
AIMS/HYPOTHESIS: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique multicentre biobank of human islets and pancreas tissues from organ donors and metabolically phenotyped pancreatectomised patients (PPP)...
November 28, 2017: Diabetologia
https://www.readbyqxmd.com/read/29183809/the-effects-of-high-glucose-exposure-on-global-gene-expression-and-dna-methylation-in-human-pancreatic-islets
#17
Elin Hall, Marloes Dekker Nitert, Petr Volkov, Siri Malmgren, Hindrik Mulder, Karl Bacos, Charlotte Ling
BACKGROUND: Type 2 diabetes (T2D) is a complex disease characterised by chronic hyperglycaemia. The effects of elevated glucose on global gene expression in combination with DNA methylation patterns have not yet been studied in human pancreatic islets. Our aim was to study the impact of 48 h exposure to high (19 mM) versus control (5.6 mM) glucose levels on glucose-stimulated insulin secretion, gene expression and DNA methylation in human pancreatic islets. RESULTS: While islets kept at 5...
November 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29181661/role-of-sertoli-and-leydig-cells-in-the-regulation-of-spermatogonial-stem-cell-and-development-of-reproductive-disorders-in-male-c57bl-6-mice-with-type-1-diabetes-mellitus
#18
E G Skurikhin, A V Pakhomova, O V Pershina, V A Krupin, N N Ermakova, E S Pan, A I Kudryashova, L A Ermolaeva, E S Khmelevskaya, V E Goldberg, V V Zhdanov, A M Dygai
Course administration streptozotocin to male C57Bl/6 mice induces a complex of symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin deficiency, focal inflammatory infiltration of the pancreas, destructive changes in the Langerhans islets, damage to the insular apparatus (reduced number of PDX1+ cells and insulin expression by the secreting cells). Male reproductive disorder are serious complications of type 1 diabetes mellitus. In "diabetic" mice, interstitial edema with inflammatory infiltration and microvascular disorders in the testicular tissue are observed, the number of endothelial precursors (CD45-/CD31+) and the total number and percentage of motile spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of into the lumen of the tubules...
November 27, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29157981/foxo1-inhibition-promotes-differentiation-of-human-embryonic-stem-cells-into-insulin-producing-cells
#19
Fei Yu, Rui Wei, Jin Yang, Junling Liu, Kun Yang, Haining Wang, Yiming Mu, Tianpei Hong
Insulin-producing cells (IPCs) derived from human embryonic stem cells (hESCs) hold great potential for cell transplantation therapy in diabetes. Tremendous progress has been made in inducing differentiation of hESCs into IPCs in vitro, of which definitive endoderm (DE) protocol mimicking foetal pancreatic development has been widely used. However, immaturity of the obtained IPCs limits their further applications in treating diabetes. Forkhead box O1 (FoxO1) is involved in the differentiation and functional maintenance of murine pancreatic β cells, but its role in human β cell differentiation is under elucidation...
November 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29142904/kras-g12d-upregulates-notch-signaling-to-induce-gallbladder-tumorigenesis-in-mice
#20
Wen-Cheng Chung, Junqing Wang, Yunyun Zhou, Keli Xu
Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context. Methods: We determined Cre recombination activity of Pdx1-Cre in the gallbladder using a reporter strain and examined gallbladder tumor development in the Kras(LSL- G12D/+);Pdx1-Cre mice...
September 2017: Oncoscience
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