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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/28724742/the-myokine-irisin-is-released-in-response-to-saturated-fatty-acids-and-promotes-pancreatic-beta-cell-survival-and-insulin-secretion
#1
Annalisa Natalicchio, Nicola Marrano, Giuseppina Biondi, Rosaria Spagnuolo, Rossella Labarbuta, Immacolata Porreca, Angelo Cignarelli, Marco Bugliani, Piero Marchetti, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
This study explored the role of irisin as a new pancreatic beta-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic beta-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner, and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic beta-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling...
July 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#2
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28674658/confluence-does-not-affect-the-expression-of-mir-375-and-its-direct-targets-in-rat-and-human-insulin-secreting-cell-lines
#3
Jones K Ofori, Helena A Malm, Ines G Mollet, Lena Eliasson, Jonathan Lou S Esguerra
MicroRNAs are small non-coding RNAs, which negatively regulate the expression of target genes. They have emerged as important modulators in beta cell compensation upon increased metabolic demand, failure of which leads to reduced insulin secretion and type 2 diabetes. To elucidate the function of miRNAs in beta cells, insulin-secreting cell lines, such as the rat insulinoma INS-1 832/13 and the human EndoC-βH1, are widely used. Previous studies in the cancer field have suggested that miRNA expression is influenced by confluency of adherent cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28672957/involvement-of-receptor-interacting-protein-140-in-palmitate-stimulated-macrophage-infiltration-of-pancreatic-beta-cells
#4
Runmei Zou, Junli Xue, Qi Huang, Zhe Dai, Yancheng Xu
Receptor-interacting protein 140 (RIP140) in macrophages stimulates the nuclear factor-κB subunit RelA to activate tumor necrosis factor (TNF)-α and interleukin (IL)-6 transcription. However, under lipotoxic conditions, the involvement of RIP140 in the infiltration of beta cells by macrophages remains unknown. In the present study, murine RAW264.7 macrophages were transfected with a RIP140 overexpression plasmid or siRNA prior to macrophage activation with 500 µM palmitate. Palmitate-free conditioned media was then collected and added to murine insulinoma MIN6 cells...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28666105/comparison-of-pancreatic-beta-cells-and-alpha-cells-under-hyperglycemia-inverse-coupling-in-pakt-foxo1
#5
Mi-Kyung Kim, Hyun Mi Shin, HyeSook Jung, EunJu Lee, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Byoung Doo Rhee, Jeong Hyun Park
Type 2 diabetes manifests beta cell deficiencies and alpha cell expansion which is consistent with relative insulin deficiency and glucagon oversecretion. The effects of hyperglycemia on alpha cells are not as understood in comparison to beta cells. Hyperglycemia increases oxidative stress, which induces Akt activation or FoxO activation, depending on cell type. Several studies independently reported that FoxO1 translocations in alpha cells and beta cells were opposite. We compared the responses of pancreatic alpha cells and beta cells against hyperglycemia...
May 19, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28652605/distinct-levels-of-reactive-oxygen-species-coordinate-metabolic-activity-with-beta-cell-mass-plasticity
#6
Ezzaldin Ahmed Alfar, Dilyana Kirova, Judith Konantz, Sarah Birke, Jörg Mansfeld, Nikolay Ninov
The pancreatic beta-cells control glucose homeostasis by secreting insulin in response to nutrient intake. The number of beta-cells is under tight metabolic control, as this number increases with higher nutrient intake. However, the signaling pathways matching nutrition with beta-cell mass plasticity remain poorly defined. By applying pharmacological and genetic manipulations, we show that reactive oxygen species (ROS) regulate dose-dependently beta-cell proliferation in vivo and in vitro. In particular, reducing ROS levels in beta-cells blocks their proliferation in response to nutrients...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641522/advances-on-ppar%C3%AE-research-in-the-emerging-era-of-precision-medicine
#7
Pinyi Lu, Zhongming Zhao
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily that functions as a ligand-inducible transcription factor. It regulates glucose and lipid metabolism, immunity, and cellular growth and differentiation. Thiazolidinediones (TZDs) are potent insulin sensitizers that function by activating PPARs, with a high specificity for PPARγ. Due to their ability to preserve pancreatic beta cell function and reduce insulin resistance, TZDs have become one of the most prescribed classes of medications for type 2 diabetes (T2D) since their approval by the US Food and Drug Administration (FDA) and initial use in 1997...
June 21, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28631500/pancreatic-%C3%AE-cell-survival-and-proliferation-are-promoted-by-protein-kinase-g-type-i%C3%AE-and-downstream-regulation-of-akt-foxo1
#8
Janica C Wong, Van Vo, Priyatham Gorjala, Ronald R Fiscus
Early studies showed nitric oxide as a pro-inflammatory-cytokine-induced toxin involved in pancreatic β-cell destruction during pathogenesis of type-1 diabetes. However, nitric oxide has both cytotoxic and cytoprotective effects on mammalian cells, depending on concentration and micro-environmental surroundings. Our studies have shown that low/physiological-level nitric oxide selectively activates protein kinase G type Iα isoform, promoting cytoprotective/pro-cell-survival effects in many cell types. In bone marrow-derived stromal/mesenchymal stem cells, protein kinase G type Iα mediates autocrine effects of nitric oxide and atrial natriuretic peptide, promoting DNA-synthesis/proliferation and cell survival...
June 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28591745/disc1-overexpression-promotes-non-small-cell-lung-cancer-cell-proliferation
#9
Shuo Wang, Ying-Ying Chen, Yu-Peng Li, Jun Gu, Shu-Dong Gu, Hai Shi, Xue-Song Li, Xiao-Ning Lu, Xiang Li, Shuang-Long Zhang, Kang-Jun Yu, Kun Liu, Li-Li Ji
Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/β-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and may promote neural progenitor cell and pancreatic β-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3β, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28504695/epigenetic-pathway-inhibitors-represent-potential-drugs-for-treating-pancreatic-and-bronchial-neuroendocrine-tumors
#10
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
#11
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
#12
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
#13
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 α-subunit of the heterotrimeric Gz protein, Gαz, promotes β-cell death and inhibits β-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional β-cell mass in the nonobese 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...
June 1, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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