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Pdx1 AND Beta cells

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https://www.readbyqxmd.com/read/29772703/alpha-mangostin-improves-insulin-secretion-and-protects-ins-1-cells-from-streptozotocin-induced-damage
#1
Dahae Lee, Young-Mi Kim, Kiwon Jung, Young-Won Chin, Ki Sung Kang
Alpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen ( Garcinia mangostana ), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1⁻10 μM) and its impact on insulin signaling was examined by Western blotting...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29726111/clinical-usefulness-of-comprehensive-genetic-screening-in-mody-a-novel-abcc8-mutation-in-a-previously-screened-family
#2
Stephanie Robyn Johnson, Paul Leo, Louise Sonia Conwell, Mark Harris, Matthew Arthur Brown, Emma Letitia Duncan
Maturity-onset diabetes of the young (MODY) is the commonest form of monogenic diabetes, resulting from dominant mutations in one of fourteen genes that regulate beta-cell function (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8,KCNJ11 and APPL1 1,2 ). MODY accounts for 2-2.5% of childhood diabetes 3 , yet MODY genetic screening is uncommon, even in highly suggestive families, and when performed often limited to the commonest genes (e.g.HNF1A and GCK) 4 .
May 4, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29717223/effect-of-the-sodium-glucose-cotransporter-2-inhibitor-luseogliflozin-on-pancreatic-beta-cell-mass-in-db-db-mice-of-different-ages
#3
Kiyohiko Takahashi, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Naoyuki Kitao, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
To examine the effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on pancreatic beta cell mass in db/db mice of different ages. db/db mice aged 6, 10, 14 and 24 weeks old were fed either standard chow (control group) or standard chow containing 0.01% luseogliflozin (luseo group). After 4 weeks, immunohistochemistry and gene expression tests were conducted. In 6-week-old db/db mice, immunohistochemistry revealed a significant increase in beta cell mass in the luseo group compared with the control group after 4 weeks of treatment...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29696608/regulation-of-aging-and-oxidative-stress-pathways-in-aged-pancreatic-islets-using-alpha-lipoic-acid
#4
Navid Nobakht-Haghighi, Mahban Rahimifard, Maryam Baeeri, Mohammad Amin Rezvanfar, Shermineh Moini Nodeh, Hamed Haghi-Aminjan, Emre Hamurtekin, Mohammad Abdollahi
Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study investigates the anti-aging, anti-apoptotic, and antioxidant properties of alpha-lipoic acid (ALA), aiming to improve aged rat pancreatic cells. In this regard, half maximal effective concentration (EC50 ) of ALA based on the survival of aged pancreatic islet cells was determined as 100 µM. Following this, p38 and p53 genes expression as key factors in aging, oxidative stress biomarkers, insulin secretion, and Pdx1 protein expression were evaluated using real-time PCR, ELISA reader, and fluorescence microscope...
April 25, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29686779/valproic-acid-exposure-of-pregnant-rats-during-organogenesis-disturbs-pancreas-development-in-insulin-synthesis-and-secretion-of-the-offspring
#5
Komariah Komariah, Wasmen Manalu, Bambang Kiranadi, Adi Winarto, Ekowati Handharyani, M Orliando Roeslan
Valproic acid (VPA) plays a role in histone modifications that eventually inhibit the activity of histone deacetylase (HDAC), and will affect the expressions of genes Pdx1, Nkx6.1, and Ngn3 during pancreatic organogenesis. This experiment was designed to study the effect of VPA exposure in pregnant rats on the activity of HDAC that controls the expression of genes regulating the development of beta cells in the pancreas to synthesize and secrete insulin. This study used 30 pregnant Sprague-Dawley rats, divided into 4 groups, as follows: (1) a control group of pregnant rats without VPA administration, (2) pregnant rats administered with 250 mg VPA on day 10 of pregnancy, (3) pregnant rats administered with 250 mg VPA on day 13 of pregnancy, and (4) pregnant rats administered with 250 mg VPA on day 16 of pregnancy...
April 2018: Toxicological Research
https://www.readbyqxmd.com/read/29587416/knocking-down-insulin-receptor-in-pancreatic-beta-cell-lines-with-lentiviral-small-hairpin-rna-reduces-glucose-stimulated-insulin-secretion-via-decreasing-the-gene-expression-of-insulin-glut2-and-pdx1
#6
Jie Wang, Wenyi Gu, Chen Chen
Type 2 diabetes (T2D) is a metabolic disorder characterized by beta cell dysfunction and insulin resistance in fat, muscle and liver cells. Recent studies have shown that the development of insulin resistance in pancreatic beta cell lines may contribute to beta cell dysfunction in T2D. However, there still is a lack of detailed investigations regarding the mechanisms by which insulin deficiency may contribute in diabetes. In this study, we firstly established a stable insulin receptor knockdown cell line in pancreatic beta cells INS-1 (InsRβKD cells) using anti InsRβ small hairpin RNA (InsRβ-shRNA) encoded by lentiviral vectors...
March 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29516647/pancreatic-beta-cells-are-a-sensitive-target-of-embryonic-exposure-to-butylparaben-in-zebrafish-danio-rerio
#7
Sarah E Brown, Karilyn E Sant, Shana M Fleischman, Olivia Venezia, Monika A Roy, Ling Zhao, Alicia R Timme-Laragy
BACKGROUND: Butylparaben (butyl p-hydroxybenzoic acid) is a common cosmetic and pharmaceutical preservative reported to induce oxidative stress and endocrine disruption. Embryonic development is sensitive to oxidative stress, with redox potentials playing critical roles in progenitor cell fate decisions. Because pancreatic beta cells have been reported to have low antioxidant gene expression, they may be sensitive targets of oxidative stress. We tested the hypotheses that butylparaben causes oxidative stress in the developing embryo, and that pancreatic beta cells are a sensitive target of butylparaben embryotoxicity...
March 8, 2018: Birth Defects Research
https://www.readbyqxmd.com/read/29511614/the-combined-effect-of-pdx1-overexpression-and-shh-manipulation-on-the-function-of-insulin-producing-cells-derived-from-adipose-tissue-stem-cells
#8
Mahmoud Hashemi Tabar, Mohammad Reza Tabandeh, Eskandar Moghimipour, Dian Dayer, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
Pancreatic and duodenal homeobox 1 (Pdx1) and Sonic hedgehog (Shh) are the key regulators of beta-cell function. In vitro experiments have shown that there is significant cooperation between Pdx1 and Shh with regard to the production and maintenance of insulin-producing cells (IPCs). In this study, the combined effect of Pdx1 overexpression and Shh manipulation on the function of adipose tissue-derived IPCs was determined. A eukaryotic expression vector ( Pdx1- pCDNA3.1(+)) was constructed and transfected into a Chinese hamster ovary (CHO) cell line...
March 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29503087/functional-beta-cell-mass-from-device-encapsulated-hesc-derived-pancreatic-endoderm-achieving-metabolic-control
#9
Thomas Robert, Ines De Mesmaeker, Geert M Stangé, Krista G Suenens, Zhidong Ling, Evert J Kroon, Daniel G Pipeleers
Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. Human embryonic stem cell-derived pancreatic endoderm (hES-PE) can generate implants with glucose-responsive beta cells capable of reducing hyperglycemia in mice. This study with device-encapsulated hES-PE (4 × 106 cells/mouse) determines the biologic characteristics at which implants establish metabolic control during a 50-week follow-up. A metabolically adequate FBM was achieved by (1) formation of a sufficient beta cell number (>0...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29453918/high-dose-of-histone-deacetylase-inhibitors-affects-insulin-secretory-mechanism-of-pancreatic-beta-cell-line
#10
Eiji Yamato
OBJECTIVE: Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of the lysine residue of proteins, including histones, and regulate the transcription of a variety of genes. Recently, HDACis have been used clinically as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have been proven to protect the cytokine-induced damage of pancreatic beta cells, evidence also shows that high doses of HDACis are cytotoxic. In the present study, we, therefore, investigated the eff ect of HDACis on insulin secretion in a pancreatic beta cell line...
January 1, 2018: Endocrine Regulations
https://www.readbyqxmd.com/read/29428671/swertisin-ameliorates-diabetes-by-triggering-pancreatic-progenitors-for-islet-neogenesis-in-streptozotocin-treated-balb-c-mice
#11
Abhay Srivastava, Nidheesh Dadheech, Mitul Vakani, Sarita Gupta
In the present study, Swertisin's role in triggering resident pancreatic progenitors for islet neogenesis in Streptozotocin (STZ) diabetic mice was explored. STZ diabetic mice when treated with Swertisin demonstrated reversion to normoglycemia and significant elevation of fasting serum insulin levels. On screening the pancreatic tissue post Swertisin treatment in the STZ diabetic mice, we observed significant up-regulation of key transcription factors viz. Pdx1, Neurog3, MafA and Nkx6.1 required for islet neogenesis and beta cell homeostasis...
April 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29422234/an-overview-of-type-2-diabetes-and-importance-of-vitamin-d3-vitamin-d-receptor-interaction-in-pancreatic-%C3%AE-cells
#12
REVIEW
Abraham Neelankal John, Fang-Xu Jiang
One significant health issue that plagues contemporary society is that of Type 2 diabetes (T2D). This disease is characterised by higher-than-average blood glucose levels as a result of a combination of insulin resistance and insufficient insulin secretions from the β-cells of pancreatic islets of Langerhans. Previous developmental research into the pancreas has identified how early precursor genes of pancreatic β-cells, such as Cpal, Ngn3, NeuroD, Ptf1a, and cMyc, play an essential role in the differentiation of these cells...
April 2018: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#13
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
#14
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/29289465/investigating-the-role-of-transcription-factors-of-pancreas-development-in-pancreatic-cancer
#15
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...
March 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
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)...
March 2018: Diabetologia
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#17
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107069/the-species-origin-of-the-cellular-microenvironment-influences-markers-of-beta-cell-fate-and-function-in-endoc-%C3%AE-h1-cells
#18
N Jeffery, S Richardson, C Beall, L W Harries
Interaction between islet cell subtypes and the extracellular matrix influences beta-cell function in mammals. The tissue architecture of rodent islets is very different to that of human islets; cell-to-cell communication and interaction with the extracellular matrix may vary between species. In this work, we have compared the responses of the human EndoC-βH1 cell line to non-human and human-derived growth matrices in terms of growth morphology, gene expression and glucose-stimulated insulin secretion (GSIS)...
December 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#19
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/29079704/mitochondrial-protein-ucp2-controls-pancreas-development
#20
Benjamin Broche, Selma Ben Fradj, Esther Aguilar, Tiphaine Sancerni, Matthieu Bénard, Fatna Makaci, Claire Berthault, Raphaël Scharfmann, Marie-Clotilde Alves-Guerra, Bertrand Duvillié
The mitochondrial carrier uncoupling protein (UCP) 2 belongs to the family of the UCPs. Despite its name, it is now accepted that UCP2 is rather a metabolite transporter than a UCP. UCP2 can regulate oxidative stress and/or energetic metabolism. In rodents, UCP2 is involved in the control of α- and β-cell mass as well as insulin and glucagon secretion. Our aim was to determine whether the effects of UCP2 observed on β-cell mass have an embryonic origin. Thus, we used Ucp2 knockout mice. We found an increased size of the pancreas in Ucp2 -/- fetuses at embryonic day 16...
January 2018: Diabetes
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