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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/29108266/the-systemic-tumor-response-to-rnase-a-treatment-affects-the-expression-of-genes-involved-in-maintaining-cell-malignancy
#1
Nadezhda Mironova, Olga Patutina, Evgenyi Brenner, Alexander Kurilshikov, Valentin Vlassov, Marina Zenkova
Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098149/regulation-of-ire1%C3%AE-by-the-small-molecule-inhibitor-4%C3%AE-8c-in-hepatoma-cells
#2
Claire Stewart, Andrea Estrada, Paul Kim, Dong Wang, Yuren Wei, Chris Gentile, Michael Pagliassotti
The unfolded protein response (UPR) is activated in response to impairments of the folding environment in the endoplasmic reticulum (ER). The most conserved arm of the UPR, inositol-requiring ER-to-nucleus signaling protein (IRE1α), has been linked to the regulation of a diverse array of cellular processes including ER-associated degradation, inflammatory signaling, cell proliferation and membrane biogenesis. Recent studies have utilized the selective, small molecule inhibitor, 4μ8c, to examine the role of IRE1α endoribonuclease (RNase) activity in various cell types including multiple myeloma, mouse embryonic fibroblasts and pancreatic beta cells [1-5]...
April 2017: Endoplasmic Reticulum Stress in Diseases
https://www.readbyqxmd.com/read/29068758/effects-of-biotin-supplementation-during-the-first-week-postweaning-increases-pancreatic-islet-area-beta-cell-proportion-islets-number-and-beta-cell-proliferation
#3
Wilma Tixi-Verdugo, Juan Contreras-Ramos, Gloria Sicilia-Argumedo, Michael S German, Cristina Fernandez-Mejia
During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation...
October 25, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29058819/involvement-of-dying-beta-cell-originated-messenger-molecules-in-differentiation-of-pancreatic-mesenchymal-stem-cells-under-glucotoxic-and-glucolipotoxic-conditions
#4
Selda Gezginci-Oktayoglu, Evren Onay-Ucar, Serap Sancar-Bas, Ayse Karatug-Kacar, Emine Sekure Nazli Arda, Sehnaz Bolkent
Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type2 diabetes mellitus. Pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized...
October 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29037070/melatonin-promotes-self-renewal-of-nestin-positive-pancreatic-stem-cells-through-activation-of-the-mt2-erk-smad-nestin-axis
#5
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promotion of self-renewal in pancreatic stem cells remain unknown. In this study, we incubated murine pancreatic stem cells (PSCs) with various concentrations of melatonin (0.01, 0.1, 1, 10 or 100 μM) to screen for the optimum culture medium for increasing cell proliferation. We found that 10 μM melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in PSCs via melatonin receptor 2 (MT2)...
October 16, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29029423/disc1-overexpression-promotes-non-small-cell-lung-cancer-cell-proliferation
#6
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...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28993191/the-anti-aging-protein-klotho-is-induced-by-gaba-therapy-and-exerts-protective-and-stimulatory-effects-on-pancreatic-beta-cells
#7
Gérald J Prud'homme, Yelena Glinka, Merve Kurt, Wenjuan Liu, Qinghua Wang
Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes...
December 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28982341/gastrin-a-potential-predictor-of-response-to-incretin-therapy-in-diabetes-type-2-patients
#8
Ines Bilic-Curcic, Maja Cigrovski Berkovic
BACKGROUND AND OBJECTIVES: Personalized management of diabetes has become an imperative since majority of monotherapy fails within 3 years of its use. Identifying responders from non-responders for a certain type of therapy would reduce a period of unsuccessful treatment and minimize health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response as well as slow down glucose absorption by acting on gastric emptying...
October 3, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28977937/overexpression-of-mir-135b-5p-promotes-unfavorable-clinical-characteristics-and-poor-prognosis-via-the-repression-of-sfrp4-in-pancreatic-cancer
#9
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974717/acinar-cells-in-the-neonatal-pancreas-grow-by-self-duplication-and-not-by-neogenesis-from-duct-cells
#10
Isabelle Houbracken, Luc Bouwens
Pancreatic acinar cells secrete digestive enzymes necessary for nutrient digestion in the intestine. They are considered the initiating cell type of pancreatic cancer and are endowed with differentiation plasticity that has been harnessed to regenerate endocrine beta cells. However, there is still uncertainty about the mechanisms of acinar cell formation during the dynamic period of early postnatal development. To unravel cellular contributions in the exocrine acinar development we studied two reporter mouse strains to trace the fate of acinar and duct cells during the first 4 weeks of life...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28974674/insights-into-beta-cell-regeneration-for-diabetes-via-integration-of-molecular-landscapes-in-human-insulinomas
#11
Huan Wang, Aaron Bender, Peng Wang, Esra Karakose, William B Inabnet, Steven K Libutti, Andrew Arnold, Luca Lambertini, Micheal Stang, Herbert Chen, Yumi Kasai, Milind Mahajan, Yayoi Kinoshita, Gustavo Fernandez-Ranvier, Thomas C Becker, Karen K Takane, Laura A Walker, Shira Saul, Rong Chen, Donald K Scott, Jorge Ferrer, Yevgeniy Antipin, Michael Donovan, Andrew V Uzilov, Boris Reva, Eric E Schadt, Bojan Losic, Carmen Argmann, Andrew F Stewart
Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Reasoning that insulinomas hold the "genomic recipe" for beta cell expansion, we surveyed 38 human insulinomas to obtain insights into therapeutic pathways for beta cell regeneration. An integrative analysis of whole-exome and RNA-sequencing data was employed to extensively characterize the genomic and molecular landscape of insulinomas relative to normal beta cells. Here, we show at the pathway level that the majority of the insulinomas display mutations, copy number variants and/or dysregulation of epigenetic modifying genes, most prominently in the polycomb and trithorax families...
October 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28951825/micrornas-as-stress-regulators-in-pancreatic-beta-cells-and-diabetes
#12
REVIEW
Mary P LaPierre, Markus Stoffel
BACKGROUND: MicroRNAs have emerged as important regulatory non-coding RNAs that tune cellular responses to physiological perturbations and disease conditions. An increasing body of literature underlines the important roles of miRNA function in pancreatic β-cells in response to metabolic, genetic and inflammatory stress. Lessons from genetic loss- and gain-of-function studies have implicated several highly expressed and evolutionary conserved miRNAs in stress signal modulation, resolution and buffering, thereby forming stabilizing miRNA networks that preserve β-cell differentiation, function, proliferation and cell survival...
September 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28939870/different-developmental-histories-of-beta-cells-generate-functional-and-proliferative-heterogeneity-during-islet-growth
#13
Sumeet Pal Singh, Sharan Janjuha, Theresa Hartmann, Özge Kayisoglu, Judith Konantz, Sarah Birke, Priyanka Murawala, Ezzaldin Ahmed Alfar, Kei Murata, Anne Eugster, Naoki Tsuji, Edward R Morrissey, Michael Brand, Nikolay Ninov
The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function and proliferation. Here we show that the pancreatic beta-cells in zebrafish exhibit different growth-promoting and functional properties, which in part reflect differences in the time elapsed since birth of the cells. Calcium imaging shows that the beta-cells in the embryonic islet become functional during early zebrafish development...
September 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28914811/leptolide-improves-insulin-resistance-in-diet-induced-obese-mice
#14
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
#15
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
#16
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
#17
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
#18
Aida I Sacaan, Stephane Thibault, Miyoun Hong, Nagesha G Kondegowda, Tim Nichols, Rosemary Li, Carolina Rosselot, Winston Evering, Rafael Fenutria, Allison Vitsky, Thomas Brown, Martin Finkelstein, Adolfo Garcia-Ocaña, Nasir 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
#19
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
#20
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
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