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Pdx1 AND Beta cells

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https://www.readbyqxmd.com/read/28534195/identification-of-a-small-molecule-that-facilitates-the-differentiation-of-human-ipscs-escs-and-mouse-embryonic-pancreatic-explants-into-pancreatic-endocrine-cells
#1
Yasushi Kondo, Taro Toyoda, Ryo Ito, Michinori Funato, Yoshiya Hosokawa, Satoshi Matsui, Tomomi Sudo, Masahiro Nakamura, Chihiro Okada, Xiaotong Zhuang, Akira Watanabe, Akira Ohta, Nobuya Inagaki, Kenji Osafune
AIMS/HYPOTHESIS: Pancreatic beta-like cells generated from human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells (hESCs) offer an appealing donor tissue source. However, differentiation protocols that mainly use growth factors are costly. Therefore, in this study, we aimed to establish efficient differentiation protocols to change hiPSCs/hESCs to insulin (INS)(+) cells using novel small-molecule inducers. METHODS: We screened small molecules that increased the induction rate of INS(+) cells from hESC-derived pancreatic and duodenal homeobox 1 (PDX1)(+) pancreatic progenitor cells...
May 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28469576/plant-produced-asialo-erythropoietin-restores-pancreatic-beta-cell-function-by-suppressing-mammalian-sterile-20-like-kinase-mst1-and-caspase-3-activation
#2
Elena Arthur, Farooqahmed S Kittur, Yuan Lin, Chiu-Yueh Hung, David C Sane, Jiahua Xie
Pancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28466490/local-and-regional-control-of-calcium-dynamics-in-the-pancreatic-islet
#3
REVIEW
Guy A Rutter, David J Hodson, Pauline Chabosseau, Elizabeth Haythorne, Timothy J Pullen, Isabelle Leclerc
Ca(2+) is the key intracellular regulator of insulin secretion, acting in the beta cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K(+) channel closure and plasma membrane depolarisation engage a sophisticated machinery to drive pulsatile cytosolic Ca(2+) changes. Voltage-gated Ca(2+) channels, Ca(2+) -activated K(+) channels and Na(+) /Ca(2+) exchange all play important roles. The use of targeted Ca(2+) probes has revealed that during each cytosolic Ca(2+) pulse, uptake of Ca(2+) by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca(2+) dynamics and control organellar function...
May 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#4
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28363269/establishing-a-large-animal-model-for-in-vivo-reprogramming-of-bile-duct-cells-into-insulin-secreting-cells-to-treat-diabetes
#5
Caitlin M Hill, Anannya Banga, Juan E Abrahante, Ce Yuan, Lucas A Mutch, Jody Janecek, Timothy O'Brien, Melanie L Graham, James R Dutton
Type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. Both of these approaches have severe limitations. Repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures. Islet transplantation, while highly effective, is severely limited by shortage of donor organs...
March 31, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28270834/metabolic-stress-and-compromised-identity-of-pancreatic-beta-cells
#6
REVIEW
Avital Swisa, Benjamin Glaser, Yuval Dor
Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28152182/reprogramming-of-pancreatic-acinar-cells-to-functional-beta-cells-by-in-vivo-transduction-of-a-polycistronic-construct-containing-pdx1-ngn3-mafa-in-mice
#7
C Cavelti-Weder, A Zumsteg, W Li, Q Zhou
To generate new beta cells after birth is a key focus of regenerative medicine, which could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: (1) the development of beta cells from putative precursor cells of the adult pancreas, which is termed neogenesis, (2) replication of existing beta cells, (3) differentiation from embryonic or induced pluripotent stem cells, and (4) reprogramming of non-beta cells to beta cells. Studies from the authors' laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA...
February 2, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28095440/comprehensive-maturity-onset-diabetes-of-the-young-mody-gene-screening-in-pregnant-women-with-diabetes-in-india
#8
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/28000178/quercetin-potentiates-transdifferentiation-of-bone-marrow-mesenchymal-stem-cells-into-the-beta-cells-in-vitro
#9
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/27662780/metformin-prevents-glucotoxicity-by-alleviating-oxidative-and-er-stress-induced-cd36-expression-in-pancreatic-beta-cells
#10
Jun Sung Moon, Udayakumar Karunakaran, Suma Elumalai, In-Kyu Lee, Hyoung Woo Lee, Yong-Woon Kim, Kyu Chang Won
AIM/HYPOTHESIS: Cluster determinant 36 (CD36), a fatty acid transporter, was reported to have a pivotal role in glucotoxicity-induced beta cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression, and it is unknown whether this action can be counteracted by metformin. In the present study, we showed that metformin counteracts glucotoxicity by alleviating oxidative and endoplasmic reticulum (ER) stress-induced CD36 expression. METHODS: We used primary rat islets as well as INS-1 cells for 72h to 24h with 30mM glucose, respectively...
January 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27644314/senp2-expression-was-induced-by-chronic-glucose-stimulation-in-ins1-cells-and-it-was-required-for-the-associated-induction-of-ccnd1-and-mafa
#11
Hye Seung Jung, Yu Mi Kang, Ho Seon Park, Byung Yong Ahn, Hakmo Lee, Min Joo Kim, Jin Young Jang, Sun-Whe Kim
Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in β cells. However, the role of SUMO modification in β cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in β cell mass...
November 2016: Islets
https://www.readbyqxmd.com/read/27514733/in-vitro-differentiation-potential-of-human-haematopoietic-cd34-cells-towards-pancreatic-%C3%AE-cells
#12
Manne Mudhu Sunitha, Lokanathan Srikanth, Pasupuleti Santhosh Kumar, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
Haematopoietic stem cells (HSCs) possess multipotent ability to differentiate into various types of cells on providing appropriate niche. In the present study, the differentiating potential of human HSCs into β-cells of islets of langerhans was explored. Human HSCs were apheretically isolated from a donor and cultured. Phenotypic characterization of CD34 glycoprotein in the growing monolayer HSCs was confirmed by immunocytochemistry and flow cytometry techniques. HSCs were induced by selection with beta cell differentiating medium (BDM), which consists of epidermal growth factor (EGF), fibroblast growth factor (FGF), transferrin, Triiodo-l-Tyronine, nicotinamide and activin A...
October 2016: Cell Biology International
https://www.readbyqxmd.com/read/27388217/islet-pericytes-are-required-for-%C3%AE-cell-maturity
#13
Adi Sasson, Eleonor Rachi, Lina Sakhneny, Daria Baer, Michal Lisnyansky, Alona Epshtein, Limor Landsman
β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to β-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin-based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression...
October 2016: Diabetes
https://www.readbyqxmd.com/read/27374092/%C3%AE-mscs-successful-fusion-of-mscs-with-%C3%AE-cells-results-in-a-%C3%AE-cell-like-phenotype
#14
Zahra Azizi, Claudia Lange, Federico Paroni, Amin Ardestani, Anke Meyer, Yonghua Wu, Axel R Zander, Christof Westenfelder, Kathrin Maedler
Bone marrow mesenchymal stromal cells (MSC) have anti-inflammatory, anti-apoptotic and immunosuppressive properties and are a potent source for cell therapy. Cell fusion has been proposed for rapid generation of functional new reprogrammed cells. In this study, we aimed to establish a fusion protocol of bone marrow-derived human MSCs with the rat beta-cell line (INS-1E) as well as human isolated pancreatic islets in order to generate insulin producing beta-MSCs as a cell-based treatment for diabetes.Human eGFP+ puromycin+ MSCs were co-cultured with either stably mCherry-expressing rat INS-1E cells or human dispersed islet cells and treated with phytohemagglutinin (PHA-P) and polyethylene glycol (PEG) to induce fusion...
August 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27270601/the-spatiotemporal-pattern-of-glis3-expression-indicates-a-regulatory-function-in-bipotent-and-endocrine-progenitors-during-early-pancreatic-development-and-in-beta-pp-and-ductal-cells
#15
Hong Soon Kang, Yukimasa Takeda, Kilsoo Jeon, Anton M Jetten
The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11...
2016: PloS One
https://www.readbyqxmd.com/read/27243814/generation-of-functional-beta-like-cells-from-human-exocrine-pancreas
#16
Maria J Lima, Kenneth R Muir, Hilary M Docherty, Neil W A McGowan, Shareen Forbes, Yves Heremans, Harry Heimberg, John Casey, Kevin Docherty
Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells...
2016: PloS One
https://www.readbyqxmd.com/read/27181524/pancreatic-differentiation-of-pdx1-gfp-reporter-mouse-induced-pluripotent-stem-cells
#17
Angelo Porciuncula, Anujith Kumar, Saray Rodriguez, Maher Atari, Miriam Araña, Franz Martin, Bernat Soria, Felipe Prosper, Catherine Verfaillie, Miguel Barajas
Efficient induction of defined lineages in pluripotent stem cells constitutes the determinant step for the generation of therapeutically relevant replacement cells to potentially treat a wide range of diseases, including diabetes. Pancreatic differentiation has remained an important challenge in large part because of the need to differentiate uncommitted pluripotent stem cells into highly specialized hormone-secreting cells, which has been shown to require a developmentally informed step-by-step induction procedure...
December 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27063289/a-programmable-synthetic-lineage-control-network-that-differentiates-human-ipscs-into-glucose-sensitive-insulin-secreting-beta-like-cells
#18
Pratik Saxena, Boon Chin Heng, Peng Bai, Marc Folcher, Henryk Zulewski, Martin Fussenegger
Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON)...
April 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27053234/mst1-a-promising-therapeutic-target-to-restore-functional-beta-cell-mass-in-diabetes
#19
REVIEW
Amin Ardestani, Kathrin Maedler
The loss of insulin-producing beta cells by apoptosis is a hallmark of all forms of diabetes mellitus. Strategies to prevent beta cell apoptosis and dysfunction are urgently needed to restore the insulin-producing cells and to prevent severe diabetes progression. We recently identified the serine/threonine kinase known as mammalian sterile 20-like kinase 1 (MST1) as a critical regulator of apoptotic beta cell death and dysfunction. MST1 activates several apoptotic signalling pathways, which further stimulate its own cleavage, leading to a vicious cycle of cell death...
September 2016: Diabetologia
https://www.readbyqxmd.com/read/26980118/differentiation-of-mouse-embryonic-stem-cells-towards-functional-pancreatic-beta-cell-surrogates-through-epigenetic-regulation-of-pdx1-by-nitric-oxide
#20
Carmen Salguero-Aranda, Rafael Tapia-Limonchi, Gladys Margot Cahuana, Ana Belen Hitos, Irene Diaz, Abdelkrim Hmadcha, Mario Fraga, Franz Martín, Bernat Soria, Juan Rigoberto Tejedo, Francisco Javier Bedoya
Pdx1 (Pancreatic and duodenal homeobox 1) is a transcription factor that regulates the embryonic development of the pancreas and the differentiation towards beta cells. Previously, we have shown that exposure of mouse embryonic stem cells (mESC) to high concentrations of NO donor diethylenetriamine nitric oxide adduct (DETA-NO) triggers differentiation events and promotes the expression of Pdx1. Here we report evidence that Pdx1 expression is associated with release of Polycomb Repressive Complex 2 (PRC2) and P300 from its promoter region...
March 14, 2016: Cell Transplantation
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