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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/28504695/epigenetic-pathway-inhibitors-represent-potential-drugs-for-treating-pancreatic-and-bronchial-neuroendocrine-tumors
#1
K E Lines, M Stevenson, P Filippakopoulos, S Müller, H E Lockstone, B Wright, S Grozinsky-Glasberg, A B Grossman, S Knapp, D Buck, C Bountra, R V Thakker
Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28485397/corrigendum-advances-in-pancreatic-islet-monolayer-culture-on-glass-surfaces-enable-super-resolution-microscopy-and-insights-into-beta-cell-ciliogenesis-and-proliferation
#2
Edward A Phelps, Chiara Cianciaruso, Jaime Santo-Domingo, Miriella Pasquier, Gabriele Galliverti, Lorenzo Piemonti, Ekaterine Berishvili, Olivier Burri, Andreas Wiederkehr, Jeffrey A Hubbell, Steinunn Baekkeskov
No abstract text is available yet for this article.
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28443133/analysis-of-purified-pancreatic-islet-beta-and-alpha-cell-transcriptomes-reveals-11%C3%AE-hydroxysteroid-dehydrogenase-hsd11b1-as-a-novel-disallowed-gene
#3
Timothy J Pullen, Mark O Huising, Guy A Rutter
We and others have previously identified a group of genes, dubbed "disallowed," whose expression is markedly lower in pancreatic islets than in other mammalian cell types. Forced mis-expression of several members of this family leads to defective insulin secretion, demonstrating the likely importance of disallowance for normal beta cell function. Up to now, transcriptomic comparisons have been based solely on data from whole islets. This raises the possibilities that (a) there may be important differences in the degree of disallowance of family members between beta and other either neuroendocrine cells; (b) beta (or alpha) cell disallowed genes may have gone undetected...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28419211/the-inhibitory-g-protein-%C3%AE-subunit-g%C3%AE-z-promotes-type-1-diabetes-like-pathophysiology-in-nod-mice
#4
Rachel J Fenske, Mark T Cadena, Quincy E Harenda, Haley N Wienkes, Kathryn Carbajal, Michael D Schaid, Erin Laundre, Allison L Brill, Nathan A Truchan, Harpreet Brar, Jaclyn Wisinski, Jinjin Cai, Timothy E Graham, Feyza Engin, Michelle E Kimple
The alpha subunit of the heterotrimeric Gz protein, Gαz, promotes beta-cell death and inhibits beta-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional beta-cell mass in the non-obese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates...
April 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28401888/advances-in-pancreatic-islet-monolayer-culture-on-glass-surfaces-enable-super-resolution-microscopy-and-insights-into-beta-cell-ciliogenesis-and-proliferation
#5
Edward A Phelps, Chiara Cianciaruso, Jaime Santo-Domingo, Miriella Pasquier, Gabriele Galliverti, Lorenzo Piemonti, Ekaterine Berishvili, Olivier Burri, Andreas Wiederkehr, Jeffrey A Hubbell, Steinunn Baekkeskov
A robust and reproducible method for culturing monolayers of adherent and well-spread primary islet cells on glass coverslips is required for detailed imaging studies by super-resolution and live-cell microscopy. Guided by an observation that dispersed islet cells spread and adhere well on glass surfaces in neuronal co-culture and form a monolayer of connected cells, we demonstrate that in the absence of neurons, well-defined surface coatings combined with components of neuronal culture media collectively support robust attachment and growth of primary human or rat islet cells as monolayers on glass surfaces...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28380380/virgin-beta-cells-persist-throughout-life-at-a-neogenic-niche-within-pancreatic-islets
#6
Talitha van der Meulen, Alex M Mawla, Michael R DiGruccio, Michael W Adams, Vera Nies, Sophie Dólleman, Siming Liu, Amanda M Ackermann, Elena Cáceres, Anna E Hunter, Klaus H Kaestner, Cynthia J Donaldson, Mark O Huising
Postnatal maintenance or regeneration of pancreatic beta cells is considered to occur exclusively via the replication of existing beta cells, but clinically meaningful restoration of human beta cell mass by proliferation has never been achieved. We discovered a population of immature beta cells that is present throughout life and forms from non-beta precursors at a specialized micro-environment or "neogenic niche" at the islet periphery. These cells express insulin, but lack other key beta cell markers, and are transcriptionally immature, incapable of sensing glucose, and unable to support calcium influx...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380361/efficient-generation-of-glucose-responsive-beta-cells-from-isolated-gp2-human-pancreatic-progenitors
#7
Jacqueline Ameri, Rehannah Borup, Christy Prawiro, Cyrille Ramond, Karen A Schachter, Raphael Scharfmann, Henrik Semb
Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2) as a specific cell surface marker for isolating pancreatic endoderm cells (PECs) from differentiated hESCs and human fetal pancreas...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28349057/interleukin-9-promotes-pancreatic-cancer-cells-proliferation-and-migration-via-the-mir-200a-beta-catenin-axis
#8
Bangli Hu, Huang Qiu-Lan, Rong-E Lei, Cheng Shi, Hai-Xing Jiang, Shan-Yu Qin
Background. Both IL-9 and miR-200a are involved in the pathogenesis of cancers; however, the role of IL-9 in pancreatic cancer and the possible underlying mechanisms remain unknown. The aim of this study was to investigate the effect of IL-9 on pancreatic cancer cells and its interaction with miR-200a. Methods. Pancreatic cancer cells (PANC-1 and AsPC-1) were treated with IL-9 and the expression of miR-200a and β-catenin in pancreatic cancer cells was measured. β-Catenin was examined as a target gene of miR-200a in pancreatic cancer cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28319674/assessment-of-circulating-betatrophin-concentrations-in-lean-glucose-tolerant-women-with-polycystic-ovary-syndrome
#9
Onur Erol, Mustafa Kemal Özel, Hamit Yaşar Ellidağ, Tayfun Toptaş, Aysel Uysal Derbent, Necat Yılmaz
The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m(2)) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled...
March 20, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28283396/biochemical-relationships-between-bone-turnover-markers-and-blood-glucose-in-patients-with-type-2-diabetes-mellitus
#10
Rasha M Hussein
INTRODUCTION: Patients with type 2 diabetes mellitus develop many complications including osteopenia, which is associated with high fracture risk. Osteocalcin is a non collagenous protein derived from the osteoblasts. Recently, it was found that osteocalcin enhances the pancreatic beta cell proliferation, insulin secretion and protection against type 2 diabetes. OBJECTIVE: Investigation of the association of serum osteocalcin and other bone turnover markers with blood glucose level and diabetes mellitus duration in type 2 diabetic patients...
March 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28280900/paracrine-gaba-and-insulin-regulate-pancreatic-alpha-cell-proliferation-in-a-mouse-model-of-type-1-diabetes
#11
Allen L Feng, Yun-Yan Xiang, Le Gui, Gesthika Kaltsidis, Qingping Feng, Wei-Yang Lu
AIMS/HYPOTHESIS: This study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in conditions corresponding to type 1 diabetes in a mouse model and in vitro. METHODS: Type 1 diabetes was induced by injecting the mice with streptozotocin (STZ)...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28271032/bezafibrate-ameliorates-diabetes-via-reduced-steatosis-and-improved-hepatic-insulin-sensitivity-in-diabetic-tallyho-mice
#12
Andras Franko, Susanne Neschen, Jan Rozman, Birgit Rathkolb, Michaela Aichler, Annette Feuchtinger, Laura Brachthäuser, Frauke Neff, Marketa Kovarova, Eckhard Wolf, Helmut Fuchs, Hans-Ulrich Häring, Andreas Peter, Martin Hrabě de Angelis
OBJECTIVE: Recently, we have shown that Bezafibrate (BEZ), the pan-PPAR (peroxisome proliferator-activated receptor) activator, ameliorated diabetes in insulin deficient streptozotocin treated diabetic mice. In order to study whether BEZ can also improve glucose metabolism in a mouse model for fatty liver and type 2 diabetes, the drug was applied to TallyHo mice. METHODS: TallyHo mice were divided into an early (ED) and late (LD) diabetes progression group and both groups were treated with 0...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28270438/menin-and-prmt5-suppress-glp1-receptor-transcript-and-pka-mediated-phosphorylation-of-foxo1-and-creb
#13
Abdul Bari Muhammad, Bowen Xing, Chengyang Liu, Ali Naji, Xiaosong Ma, Rebecca A Simmons, Xianxin Hua
Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic beta cell proliferation. Tamoxifen inducible deletion of multiple endocrine neoplasia type 1 (MEN1) gene, which encodes the protein menin, increases beta cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of beta cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling...
March 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28254488/the-small-rna-mir-375-a-pancreatic-islet-abundant-mirna-with-multiple-roles-in-endocrine-beta-cell-function
#14
Lena Eliasson
The pathophysiology of diabetes is complex and recent research put focus on the pancreatic islets of Langerhans and the insulin-secreting beta cells as central in the development of the disease. MicroRNAs (miRNAs), the small non-coding RNAs regulating post-transcriptional gene expression, are significant regulators of beta cell function. One of the most abundant miRNAs in the islets is miR-375. This review focus on the role of miR-375 in beta cell function, including effects in development and differentiation, proliferation and regulation of insulin secretion...
February 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28196027/mk2461-a-multitargeted-kinase-inhibitor-suppresses-the-progression-of-pancreatic-cancer-by-disrupting-the-interaction-between-pancreatic-cancer-cells-and-stellate-cells
#15
Koetsu Inoue, Hideo Ohtsuka, Masanori Tachikawa, Fuyuhiko Motoi, Masahiro Shijo, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno, Tetsuya Terasaki
OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRβ) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRβ, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRβ and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28144955/hypothyroidism-in-utero-stimulates-pancreatic-beta-cell-proliferation-and-hyperinsulinaemia-in-the-ovine-fetus-during-late-gestation
#16
Shelley E Harris, Miles J De Blasio, Melissa A Davis, Amy C Kelly, Hailey M Davenport, F B Peter Wooding, Dominique Blache, David Meredith, Miranda Anderson, Abigail L Fowden, Sean W Limesand, Alison J Forhead
KEY POINTS: Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation...
January 31, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#17
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
May 2017: Diabetologia
https://www.readbyqxmd.com/read/28069397/influence-of-neuropeptide-y-and-pancreatic-polypeptide-on-islet-function-and-beta-cell-survival
#18
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
BACKGROUND: In the present study we assessed the impact of neuropeptide Y receptor (NPYR) modulators, neuropeptide Y (NPY) and pancreatic polypeptide (PP), on islet function and beta-cell survival. METHODS: The effects of NPY and PP on beta-cell function were examined in BRIN BD11 and 1.1B4 beta-cells, as well as isolated mouse islets. Involvement of both peptides in pancreatic islet adaptations to streptozotocin and hydrocortisone, as well as effects on beta-cell proliferation and apoptosis was also evaluated...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#19
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#20
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
March 30, 2017: European Journal of Pharmaceutical Sciences
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