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Pax4 AND beta cell mass

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https://www.readbyqxmd.com/read/26813254/pax4-preserves-endoplasmic-reticulum-integrity-preventing-beta-cell-degeneration-in-a-mouse-model-of-type-1-diabetes-mellitus
#1
José Manuel Mellado-Gil, Carmen María Jiménez-Moreno, Alejandro Martin-Montalvo, Ana Isabel Alvarez-Mercado, Esther Fuente-Martin, Nadia Cobo-Vuilleumier, Petra Isabel Lorenzo, Eva Bru-Tari, Irene de Gracia Herrera-Gómez, Livia López-Noriega, Javier Pérez-Florido, Javier Santoyo-López, Andreas Spyrantis, Paolo Meda, Bernhard O Boehm, Ivan Quesada, Benoit R Gauthier
AIMS/HYPOTHESIS: A strategy to enhance pancreatic islet functional beta cell mass (BCM) while restraining inflammation, through the manipulation of molecular and cellular targets, would provide a means to counteract the deteriorating glycaemic control associated with diabetes mellitus. The aims of the current study were to investigate the therapeutic potential of such a target, the islet-enriched and diabetes-linked transcription factor paired box 4 (PAX4), to restrain experimental autoimmune diabetes (EAD) in the RIP-B7...
April 2016: Diabetologia
https://www.readbyqxmd.com/read/26193220/human-placenta-stem-cell-source-for-obtaining-pancreatic-progenitors
#2
Sergiu Şuşman, Dan Rus-Ciucă, Olga Soriţău, Răzvan Ciortea, Mihai Gîrlovanu, Dan Mihu, Carmen Mihaela Mihu
OBJECTIVES: The apparition of sugar diabetes is produced by the decrease of the number and capacity of beta cells to secrete insulin. Cell mass recovery through cell therapy might be one of the solutions for treating this disease. The use of various cell sources of different differentiation grades has been tried over the last years. Decoding the molecular mechanisms of the pancreatic morphogenesis is essential for obtaining cells having a phenotype, which would be very similar to the mature cells located in the pancreatic endocrine component...
2015: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/20448145/glial-cell-line-derived-neurotrophic-factor-enhances-neurogenin3-gene-expression-and-beta-cell-proliferation-in-the-developing-mouse-pancreas
#3
Simon M Mwangi, Yousef Usta, Shreya M Raja, Mallappa Anitha, Bindu Chandrasekharan, Alexander Parsadanian, Shanthi V Sitaraman, Shanthi Srinivasan
Glial cell line-derived neurotrophic factor (GDNF) is a factor produced by glial cells that is required for the development of the enteric nervous system. In transgenic mice that overexpress GDNF in the pancreas, GDNF has been shown to enhance beta-cell mass and improve glucose control, but the transcriptional and cellular processes involved are not known. In this study we examined the influence of GDNF on the expression of neurogenin3 (Ngn3) and other transcription factors implicated in early beta-cell development, as well as on beta-cell proliferation during embryonic and early postnatal mouse pancreas development...
July 2010: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/19665969/the-ectopic-expression-of-pax4-in-the-mouse-pancreas-converts-progenitor-cells-into-alpha-and-subsequently-beta-cells
#4
Patrick Collombat, Xiaobo Xu, Philippe Ravassard, Beatriz Sosa-Pineda, Sébastien Dussaud, Nils Billestrup, Ole D Madsen, Palle Serup, Harry Heimberg, Ahmed Mansouri
We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3...
August 7, 2009: Cell
https://www.readbyqxmd.com/read/18687378/pancreatic-transcription-factors-and-their-role-in-the-birth-life-and-survival-of-the-pancreatic-beta-cell
#5
REVIEW
Andreia S Bernardo, Colin W Hay, Kevin Docherty
In recent years major progress has been made in understanding the role of transcription factors in the development of the endocrine pancreas in the mouse. Here we describe how a number of these transcription factors play a role in maintaining the differentiated phenotype of the beta cell, and in the mechanisms that allow the beta cell to adapt to changing metabolic demands that occur throughout life. Amongst these factors, Pdx1 plays a critical role in defining the region of the primitive gut that will form the pancreas, Ngn3 expression drives cells towards an endocrine lineage, and a number of additional proteins including Pdx1, in a second wave of expression, Pax4, NeuroD1/beta2, and MafA act as beta cell differentiation factors...
November 6, 2008: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/18234907/a-focus-on-the-role-of-pax4-in-mature-pancreatic-islet-beta-cell-expansion-and-survival-in-health-and-disease
#6
REVIEW
Thierry Brun, Benoit R Gauthier
Blood glucose homeostasis is achieved by the regulation of insulin and glucagon secretion from the pancreatic islet beta- and alpha-cells. Diabetes mellitus, which comprises a heterogeneous group of hyperglycaemic disorders, results mainly from inadequate mass and function of islet beta-cells. Autoimmune destruction of beta-cells causes type 1 diabetes, while type 2 is characterized by impaired insulin secretion and is often associated with diminished insulin action on its target tissues. Interestingly, similar to type 1 diabetes, a gradual loss of beta-cell mass is observed in type 2 diabetes often requiring insulin therapy...
February 2008: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/17717131/detection-of-amplifiable-mrna-extracellular-to-insulin-producing-cells-potential-for-predicting-beta-cell-mass-and-function
#7
Sweta Rani, Martin Clynes, Lorraine O'Driscoll
BACKGROUND: Detecting extracellular nucleic acids in the serum/plasma of cancer patients may help in cancer diagnosis. We investigated whether extracellular mRNAs are reproducibly detectable in conditioned medium (CM) from insulin-producing cell cultures and if their presence and amounts are indicative of cell number and/or function. METHODS: We isolated mRNA from medium conditioned by the culture of several insulin-producing cell types: MIN6(L) (glucose-responsive), MIN6(H) (glucose-nonresponsive), and MIN6 B1 murine beta cells and monkey kidney fibroblast cells engineered to produce human preproinsulin (PPI) (Vero-PPI)...
November 2007: Clinical Chemistry
https://www.readbyqxmd.com/read/15604203/minireview-transcriptional-regulation-in-pancreatic-development
#8
REVIEW
Joel F Habener, Daniel M Kemp, Melissa K Thomas
Considerable progress has been made in the understanding of the sequential activation of signal transduction pathways and the expression of transcription factors during pancreas development. Much of this understanding has been obtained by analyses of the phenotypes of mice in which the expression of key genes has been disrupted (knockout mice). Knockout of the genes for Pdx1, Hlxb9, Isl1, or Hex results in an arrest of pancreas development at a very early stage (embryonic d 8-9). Disruption of genes encoding components of the Notch signaling pathway, e...
March 2005: Endocrinology
https://www.readbyqxmd.com/read/15596543/the-diabetes-linked-transcription-factor-pax4-promotes-beta-cell-proliferation-and-survival-in-rat-and-human-islets
#9
Thierry Brun, Isobel Franklin, Luc St-Onge, Anna Biason-Lauber, Eugene J Schoenle, Claes B Wollheim, Benoit R Gauthier
The mechanism by which the beta-cell transcription factor Pax4 influences cell function/mass was studied in rat and human islets of Langerhans. Pax4 transcripts were detected in adult rat islets, and levels were induced by the mitogens activin A and betacellulin. Wortmannin suppressed betacellulin-induced Pax4 expression, implicating the phosphatidylinositol 3-kinase signaling pathway. Adenoviral overexpression of Pax4 caused a 3.5-fold increase in beta-cell proliferation with a concomitant 1.9-, 4-, and 5-fold increase in Bcl-xL (antiapoptotic), c-myc, and Id2 mRNA levels, respectively...
December 20, 2004: Journal of Cell Biology
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