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Pancreatic beta cells

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https://www.readbyqxmd.com/read/28649880/understanding-type-1-diabetes-through-proteomics
#1
Inne Crèvecoeur, Saurabh Vig, Chantal Mathieu, Lut Overbergh
Auto-immunity against pancreatic beta-cells leads to an absolute shortage of the hormone insulin, resulting in hyperglycemia and the onset of type 1 diabetes (T1D). Proteomic approaches have been used to elucidate the mechanisms of beta-cell dysfunction and death. Areas covered: In the present review, we discuss discoveries in the beta-cell proteome that have contributed to better insights in the role of the beta-cell in T1D. Techniques, such as 2D-DIGE and MALDI imaging, together with new approaches for sample preparation, including laser capture microdissection and immunopeptidomics, have resulted in novel mechanistic insights in the pathogenesis of T1D...
June 26, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28649475/solid-pseudopapillary-tumor-of-the-pancreas-an-unusual-cause-of-abdominal-pain
#2
Talal El Imad, Fady G Haddad, Mayurathan Kesavan, Liliane Deeb, Sherif Andrawes
Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor that accounts for less than one percent of pancreatic tumors. The diagnosis could be challenging as SPN tend to manifest with nonspecific abdominal symptoms, variable radiological features, and inconsistent morphology. The cellular origin of SPN is unclear and might involve ductal, acinar and endocrine stem cells.  We report a rare case of a 27-year-old female who presented with intermittent abdominal pain for two years, associated with a decrease in appetite...
May 16, 2017: Curēus
https://www.readbyqxmd.com/read/28648619/nuclear-import-of-glucokinase-in-pancreatic-beta-cells-is-mediated-by-a-nuclear-localization-signal-and-modulated-by-sumoylation
#3
Bente Berg Johansson, Karianne Fjeld, Marie Holm Solheim, Jun Shirakawa, Enming Zhang, Magdalena Keindl, Jiang Hu, Andreas Lindqvist, Anne Døskeland, Gunnar Mellgren, Torgeir Flatmark, Pål Rasmus Njølstad, Rohit N Kulkarni, Nils Wierup, Ingvild Aukrust, Lise Bjørkhaug
The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we here present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ((30)LKKVMRR(36)) in the human enzyme...
June 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#4
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28641522/advances-on-ppar%C3%AE-research-in-the-emerging-era-of-precision-medicine
#5
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/28633420/pancreas-fat-and-beta-cell-mass-in-humans-with-and-without-diabetes-an-analysis-in-the-japanese-population
#6
Rie Murakami, Yoshifumi Saisho, Yuusuke Watanabe, Jun Inaishi, Tami Tsuchiya, Kinsei Kou, Seiji Sato, Minoru Kitago, Yuko Kitagawa, Taketo Yamada, Hiroshi Itoh
Context: The mechanisms by which beta cell mass is reduced in patients with type 2 diabetes (T2DM) remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce beta cell apoptosis, leading to the development of diabetes. Objective: The aim of this study was to clarify the effects of intra-pancreatic fat on beta and alpha cell mass in humans with and without diabetes. Design, Subjects and Methods: Using our tissue database, pancreas sections of 72 Japanese non-diabetic (NDM) autopsy cases and 50 diabetic (DM) and 49 age- and BMI-matched NDM patients who underwent pancreatic surgery were analyzed...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
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
#7
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/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#8
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28626572/optical-control-of-a-receptor-linked-guanylyl-cyclase-using-a-photoswitchable-peptidic-hormone
#9
Tom Podewin, Johannes Broichhagen, Christina Frost, Dieter Groneberg, Julia Ast, Helena Meyer-Berg, Nicholas H F Fine, Andreas Friebe, Martin Zacharias, David J Hodson, Dirk Trauner, Anja Hoffmann-Röder
The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the photochromic amino acid [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is incorporated into the peptide backbone. The endogeneous hormone ANP signals via the natriuretic peptide receptor A (NPR-A) through raising intracellular cGMP concentrations, and is involved in blood pressure regulation and sodium homeostasis, as well as lipid metabolism and pancreatic function...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28625830/bioengineering-strategies-for-inducing-tolerance-in-autoimmune-diabetes
#10
Steinunn Baekkeskov, Jeffrey A Hubbell, Edward A Phelps
Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specific immunotherapy. To bridge the fields of type 1 diabetes immunology and biomaterials engineering, this article will review recent trends in the etiology of type 1 diabetes immunopathology and will focus on the contributions of emerging bioengineered strategies in the fight against beta cell autoimmunity in type 1 diabetes...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625491/insulinotropic-action-of-2-4-dinitroanilino-benzoic-acid-through-the-attenuation-of-pancreatic-beta-cell-lesions-in-diabetic-rats
#11
Humera Jahan, M Iqbal Choudhary, Mehwish Manzoor, Khalid Mohammad Khan, Shahnaz Perveen, Atta-Ur Rahman
Beta cell destruction plays a key role in the pathogenesis of type 1 diabetes mellitus. It has also been argued that beta cell mass may also be compromised in some cases of type 2 diabetes, although this is controversial. Currently, the failure of oral antidiabetic insulin secretagogue drugs to properly correct type 2 diabetes demands novel approaches in the treatment of this condition. For any condition associated with diminished beta cell function, the aim of the present study was to investigate the in vitro and in vivo antidiabetic effect in STZ-induced diabetic rats, and maximum tolerated dose (MTD) safety of novel anthranilic acid derivative, 2, 4-dinitroanilino-benzoic acid (1)...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28617859/co-localization-of-acinar-markers-and-insulin-in-pancreatic-cells-of-subjects-with-type-2-diabetes
#12
Matilde Masini, Lorella Marselli, Eddy Himpe, Luisa Martino, Marco Bugliani, Mara Suleiman, Ugo Boggi, Franco Filipponi, Margherita Occhipinti, Luc Bouwens, Vincenzo De Tata, Piero Marchetti
To search for clues suggesting that beta cells may generate by transdifferentiation in humans, we assessed the presence of cells double positive for exocrine (amylase, carboxypeptidase A) and endocrine (insulin) markers in the pancreas of non-diabetic individuals (ND) and patients with type 2 diabetes (T2D). Samples from twelve ND and twelve matched T2D multiorgan donors were studied by electron microscopy, including amylase and insulin immunogold labeling; carboxypeptidase A immunofluorescence light microscopy assessment was also performed...
2017: PloS One
https://www.readbyqxmd.com/read/28617856/the-associations-between-vdr-bsmi-polymorphisms-and-risk-of-vitamin-d-deficiency-obesity-and-insulin-resistance-in-adolescents-residing-in-a-tropical-country
#13
Rayinda Rahmadhani, Nur Lisa Zaharan, Zahurin Mohamed, Foong Ming Moy, Muhammad Yazid Jalaludin
BACKGROUND: The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance. AIMS: This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country...
2017: PloS One
https://www.readbyqxmd.com/read/28615694/selective-serotonin-reuptake-inhibitor-fluoxetine-impairs-e-cadherin-mediated-cell-adhesion-and-alters-calcium-homeostasis-in-pancreatic-beta-cells
#14
Huang-Yu Chang, Shu-Ling Chen, Meng-Ru Shen, Mei-Lang Kung, Lee-Ming Chuang, Yun-Wen Chen
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mood disorders. Long term use of SSRIs is associated with an increased risk of diabetes, but the underlying mechanism(s) remains elusive. E-cadherin-mediated cell-cell adhesion and elevated [Ca(2+)]i are important for insulin release and pancreatic β cell functions. This study aims to investigate whether a SSRI, fluoxetine (Prozac), induces pancreatic β cell dysfunction through affecting E-cadherin and/or [Ca(2+)]i...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612706/autophagy-and-its-link-to-type-ii-diabetes-mellitus
#15
Jai-Sing Yang, Chi-Cheng Lu, Sheng-Chu Kuo, Yuan-Man Hsu, Shih-Chang Tsai, Shih-Yin Chen, Yng-Tay Chen, Ying-Ju Lin, Yu-Chuen Huang, Chao-Jung Chen, Wei-De Lin, Wen-Lin Liao, Wei-Yong Lin, Yu-Huei Liu, Jinn-Chyuan Sheu, Fuu-Jen Tsai
Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both...
June 2017: BioMedicine
https://www.readbyqxmd.com/read/28608700/a-chaotic-bursting-spiking-transition-in-a-pancreatic-beta-cells-system-observation-of-an-interior-glucose-induced-crisis
#16
Jorge Duarte, Cristina Januario, Nuno Martins
Nonlinear systems are commonly able to display abrupt qualitative changes (or transitions) in the dynamics. A particular type of these transitions occurs when the size of a chaotic attractor suddenly changes. In this article, we present such a transition through the observation of a chaotic interior crisis in the Deng bursting-spiking model for the glucose-induced electrical activity of pancreatic β-cells. To this chaos-chaos transition corresponds precisely the change between the bursting and spiking dynamics, which are central and key dynamical regimes that the Deng model is able to perform...
August 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28599824/the-clinical-characteristics-of-patients-with-mitochondrial-trna-leu-uur-m-3243a-g-mutation-compared-with-type-1-diabetes-and-early-onset-type-2-diabetes
#17
Jie Zhu, Peng Yang, Xiang Liu, Li Yan, Sharvan Rampersad, Feng Li, Hong Li, Chunjun Sheng, Xiaoyun Cheng, Manna Zhang, Shen Qu
OBJECTIVE: This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). METHODS: The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m...
April 29, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#18
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. The valproic acid, is an inhibitor of class I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
June 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28597135/glis3-rs7020673-and-rs10758593-polymorphisms-interact-in-the-susceptibility-for-type-1-diabetes-mellitus
#19
Guilherme C K Duarte, Tais S Assmann, Cristine Dieter, Bianca M de Souza, Daisy Crispim
AIMS: The transcription factor Gli-similar 3 (GLIS3) plays a key role in the development and maintenance of pancreatic beta cells as well as in the regulation of Insulin gene expression in adults. Accordingly, genome-wide association studies identified GLIS3 as a susceptibility locus for type 1 diabetes mellitus (T1DM) and glucose metabolism traits. Therefore, the aim of this study was to replicate the association of the rs10758593 and rs7020673 single nucleotide polymorphisms (SNPs) in the GLIS3 gene with T1DM in a Brazilian population...
June 9, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28591745/disc1-overexpression-promotes-non-small-cell-lung-cancer-cell-proliferation
#20
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
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