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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/28914811/leptolide-improves-insulin-resistance-in-diet-induced-obese-mice
#1
Pablo Villa-Pérez, Mercedes Cueto, Ana R Díaz-Marrero, Carmen D Lobatón, Alfredo Moreno, Germán Perdomo, Irene Cózar-Castellano
Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity...
September 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28884198/mouse-pancreatic-islet-macrophages-use-locally-released-atp-to-monitor-beta-cell-activity
#2
Jonathan R Weitz, Madina Makhmutova, Joana Almaça, Julia Stertmann, Kristie Aamodt, Marcela Brissova, Stephan Speier, Rayner Rodriguez-Diaz, Alejandro Caicedo
AIMS/HYPOTHESIS: Tissue-resident macrophages sense the microenvironment and respond by producing signals that act locally to maintain a stable tissue state. It is now known that pancreatic islets contain their own unique resident macrophages, which have been shown to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta cells communicate with islet-resident macrophages. Here we hypothesised that islet macrophages sense changes in islet activity by detecting signals derived from beta cells...
September 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28845211/oxidative-stress-in-pancreatic-beta-cell-regeneration
#3
REVIEW
Jingjing Wang, Hongjun Wang
Pancreatic β cell neogenesis and proliferation during the neonatal period are critical for the generation of sufficient pancreatic β cell mass/reserve and have a profound impact on long-term protection against type 2 diabetes (T2D). Oxidative stress plays an important role in β cell neogenesis, proliferation, and survival under both physiological and pathophysiological conditions. Pancreatic β cells are extremely susceptible to oxidative stress due to a high endogenous production of reactive oxygen species (ROS) and a low expression of antioxidative enzymes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28767692/insulin-receptor-signaling-and-glucagon-like-peptide-1-effects-on-pancreatic-beta-cells
#4
Nunzia Caporarello, Cristina Parrino, Vincenzo Trischitta, Lucia Frittitta
Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i...
2017: PloS One
https://www.readbyqxmd.com/read/28760782/cdk4-6-inhibition-on-glucose-and-pancreatic-beta-cell-homeostasis-in-young-and-aged-rats
#5
Aida I Sacaan, Stephane Thibault, Miyoun Hong, Nagesha G Kondegowda, Timothy C Nichols, Rosemary Li, Carolina Rosselot, Winston Evering, Rafael Fenutria, Allison Vitsky, Thomas Brown, Martin B Finkelstein, Adolfo Garcia-Ocaña, Nasir K Khan, Andrew F Stewart, Rupangi C Vasavada
Genetic deletion of cyclin-dependent kinase 4 (CDK4) is associated with pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one of the first selective CDK4/6 inhibitors approved for the treatment of advanced breast cancer, is currently being investigated as an adjuvant treatment in patients with early-stage breast cancer and in a variety of cancers covering a wide-range of patient populations. Hence, longer chronic toxicity studies were necessary to further examine its safety profile...
July 31, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28754856/overexpression-of-mir-135b-5p-promotes-unfavorable-clinical-characteristics-and-poor-prognosis-via-the-repression-of-sfrp4-in-pancreatic-cancer
#6
Xu Han, Hexige Saiyin, Junjie Zhao, Yuan Fang, Yefei Rong, Chenye Shi, Wenhui Lou, Tiantao Kuang
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and malignant neoplasm. The aberrant expression of miR-135b-5p and secreted frizzled-related protein 4 (SFRP4) has been revealed to be involved in various cancers. However, the clinical significance of miR-135b-5p and that of its potential target SFRP4 in PDAC remain to be elucidated. Here, we found that miR-135b-5p was markedly upregulated in pancreatic cancer tissue compared with corresponding adjacent normal tissue, whereas SFRP4 was significantly downregulated...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746825/differential-expression-of-glucagon-like-peptide-2-glp-2-is-involved-in-pancreatic-islet-cell-adaptations-to-stress-and-beta-cell-survival
#7
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
Recent studies have confirmed that locally released proglucagon derived gene products, other than glucagon, have a major influence on pancreatic endocrine function. We assessed the impact of glucagon-like peptide-2 (GLP-2) on beta-cell secretory function, proliferation and apoptosis, as well as glucose tolerance, feeding behaviour and islet adaptions to chemically-induced insulin deficiency and resistance. The GLP-2 receptor was evidenced on cultured rodent and human beta-cells, rodent alpha-cells and isolated mouse islets...
July 23, 2017: Peptides
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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