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https://www.readbyqxmd.com/read/28216051/morin-activates-the-nrf2-are-pathway-and-reduces-oxidative-stress-induced-dna-damage-in-pancreatic-beta-cells
#1
Pachamuthu Vanitha, S Senthil Kumar, Sireesh Dornadula, S Anantha Kumar, Palanisamy Rajaguru, Kunka Mohanram Ramkumar
Oxidative stress is an important factor contributing to the pathogenesis of diabetes and its complications. In our earlier study, we demonstrated the antidiabetic efficacy of morin by regulating key enzymes of carbohydrate metabolism in diabetic rats. The present study was designed to assess the antigenotoxic potential of morin in pancreatic β-cells, using the COMET assay. To explore its potential mechanisms of action, three genotoxic agents, H2O2 which induces DNA damage by the generation of reactive oxygen species, streptozotocin (STZ) by RNS and Methyl methanesulfonate (MMS) by DNA alkylation was used...
February 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28213757/germinal-centre-frequency-is-decreased-in-pancreatic-lymph-nodes-from-individuals-with-recent-onset-type-1-diabetes
#2
Abby Willcox, Sarah J Richardson, Lucy S K Walker, Sally C Kent, Noel G Morgan, Kathleen M Gillespie
AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1...
February 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28213644/circulating-micrornas-and-diabetes-mellitus-a-novel-tool-for-disease-prediction-diagnosis-and-staging
#3
REVIEW
G Sebastiani, L Nigi, G E Grieco, F Mancarella, G Ventriglia, F Dotta
Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility...
February 17, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#4
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#5
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
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
#6
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...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#7
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28193492/characterization-of-acyl-coa-synthetase-isoforms-in-pancreatic-beta-cells-gene-silencing-shows-participation-of-acsl3-and-acsl4-in-insulin-secretion
#8
Israr-Ul H Ansari, Melissa J Longacre, Scott W Stoker, Mindy A Kendrick, Lucas M O'Neill, Laura J Zitur, Luis A Fernandez, James M Ntambi, Michael J MacDonald
Long-chain acyl-CoA synthetases (ACSLs) convert fatty acids to fatty acyl-CoAs to regulate various physiologic processes. We characterized the ACSL isoforms in a cell line of homogeneous rat beta cells (INS-1 832/13 cells) and human pancreatic islets. ACSL4 and ACSL3 proteins were present in the beta cells and human and rat pancreatic islets and concentrated in insulin secretory granules and less in mitochondria and negligible in other intracellular organelles. ACSL1 and ACSL6 proteins were not seen in INS-1 832/13 cells or pancreatic islets...
February 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28182280/anti-prediabetic-effect-of-rose-hip-rosa-canina-extract-in-spontaneously-diabetic-torii-rats
#9
Si Jing Chen, Chiwa Aikawa, Risa Yoshida, Tomoaki Kawaguchi, Toshiro Matsui
BACKGROUND: Prediabetes, a high-risk state for developing diabetes showing impaired glucose tolerance but normal fasting blood glucose level, has increasing prevalence worldwide. However, no study to prevent impaired glucose tolerance at prediabetic stage by anti-diabetic functional foods has been reported. Thus, the aim of the present study was to evaluate the anti-prediabetic effect of rose hip in a prediabetic rat model. RESULTS: Spontaneously Diabetic Torii (SDT) rats were supplemented with hot-water extract of rose hip at a dose of 100 mg/kg body weight/day for 12 weeks...
February 9, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28181104/apigenin-attenuates-streptozotocin-induced-pancreatic-%C3%AE-cell-damage-by-its-protective-effects-on-cellular-antioxidant-defense
#10
Ning Wang, Wen Jing Yi, Lu Tan, Jia Hui Zhang, Jiamin Xu, Yi Chen, Mengting Qin, Shuang Yu, Jing Guan, Rui Zhang
Pancreatic beta cells are very sensitive to oxidative stress, which is one of the major causes of cell damages in diabetes. Growing interest has focused on the development of effective therapeutics to protect pancreatic cells from oxidative stress and searching for potentially protective antioxidants for treating diabetes. Apigenin, a plant-derived flavonoid, was investigated to determine whether it could protect rat insulinoma cell lines (RINm5F pancreatic beta cells) against streptozotocin (STZ)-induced oxidative damages and the mechanisms implicated...
February 8, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28179377/hepcidin-links-gluco-toxicity-to-pancreatic-beta-cell-dysfunction-through-inhibiting-pdx-1-expression
#11
Xuhua Mao, Hucheng Chen, Junmin Tang, Liangliang Wang, Tingting Shu
OBJECTIVE: Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. DESIGN: We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6...
February 8, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28178716/invasive-haemophilus-influenzae-infection-in-patients-with-cancer
#12
Vivek Singh, Sowmya Nanjappa, Smitha Pabbathi, John N Greene
A major cause of morbidity and mortality in patients with cancer is infection. Since the introduction of the Haemophilus influenzae type b (Hib) vaccine in the United States in the 1990s, invasive H influenzae infection has become less common. We report on 5 patients with cancer and invasive H influenzae infection. A literature review was also performed of the dominant Haemophilus subtype and the clinical features associated with the infection and concomitant cancer. Of the 17 cases found in the literature, had hematological malignancies and 1 case each had thymoma, schwannoma, teratoma, and pancreatic, Merkel cell, pharyngeal, laryngeal, and rectal carcinomas...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28177904/genome-scale-analysis-identifies-gjb2-and-ero1lb-as-prognosis-markers-in-patients-with-pancreatic-cancer
#13
Tao Zhu, Yuan-Feng Gao, Yi-Xin Chen, Zhi-Bin Wang, Ji-Ye Yin, Xiao-Yuan Mao, Xi Li, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174291/local-sphingosine-kinase-1-activity-improves-islet-transplantation
#14
Darling Rojas-Canales, Daniella Penko, Kay K Myo Min, Kate A Parham, Heshan Peiris, Rainer V Haberberger, Stuart M Pitson, Chris Drogemuller, Damien J Keating, Shane T Grey, Patrick T Coates, Claudine S Bonder, Claire F Jessup
Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28174288/direct-substrate-delivery-into-mitochondrial-fission-deficient-pancreatic-islets-rescues-insulin-secretion
#15
Uma D Kabra, Katrin Pfuhlmann, Adriana Migliorini, Susanne Keipert, Daniel Lamp, Olle Korsgren, Moritz Gegg, Stephen C Woods, Paul T Pfluger, Heiko Lickert, Charles Affourtit, Matthias H Tschöp, Martin Jastroch
In pancreatic beta cells, mitochondrial bioenergetics control glucose-stimulated insulin secretion (GSIS). Mitochondrial dynamics are generally associated with quality control, maintaining the functionality of bioenergetics. By acute pharmacological inhibition of mitochondrial fission protein Drp1, we here demonstrate that mitochondrial fission is necessary for GSIS in mouse and human islets. We confirm that genetic silencing of Drp1 increases mitochondrial proton leak in MIN6 cells. However, our comprehensive analysis of pancreatic islet bioenergetics reveals that Drp1 does not control insulin secretion via its effect on proton leak but instead via modulation of glucose-fuelled respiration...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28161954/two-photon-dye-cocktail-for-dual-color-3d-imaging-of-pancreatic-beta-and-alpha-cells-in-live-islets
#16
Bikram Keshari Agrawalla, Hyo Won Lee, Wut-Hmone Phue, Anandhkumar Raju, Jong-Jin Kim, Hwan Myung Kim, Nam-Young Kang, Young-Tae Chang
Insulin-secreting beta cells together with glucagon-producing alpha cells play an essential role in maintaining the optimal blood glucose level in the body, so the development of selective probes for imaging of these cell types in live islets is highly desired. Herein we report the development of a 2-glucosamine-based two-photon fluorescent probe, TP-β, that is suitable for imaging of beta cells in live pancreatic islets from mice. Flow cytometry studies confirmed that TP-β is suitable for isolation of primary beta cells...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28161382/association-of-serum-pancreatic-derived-factor-pander-with-beta-cell-dysfunction-in-type-2-diabetes-mellitus
#17
Miral M Shehata, Mohamed M Kamal, Mohamed H El-Hefnawy, Hala O El-Mesallamy
AIM: Beta-cell dysfunction is the critical determinant for type 2 diabetes. The novel PANcreatic DERived factor (PANDER) has been identified as interesting islet-secreted cytokine that might be involved in beta-cell dysfunction, a role that has n"ot been clinically elucidated yet. Therefore, this study was designed to study the potential clinical association of this cytokine with beta-cell dysfunction in type 2 diabetes. METHODS: Anthropometric parameters, routine biochemical markers and serum levels of PANDER were measured in 63 diabetic subjects including; recently diagnosed type 2 diabetic patients with duration of diabetes ≤6months and long-standing type 2 diabetic patients with duration of diabetes ≥5years then compared to 16 healthy control volunteers...
January 20, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28154952/an-immunohistochemical-study-of-nitrotyrosine-expression-in-pancreatic-islets-of-cases-with-increasing-duration-of-type-1-diabetes-and-without-diabetes
#18
Charlton Martin, Lars Krogvold, Shebani Farik, Satya Amirapu, Fiona Wu, Shiva Reddy, Knut Dahl-Jørgensen
Peroxynitrite-induced nitration of cellular proteins has been shown to associate with various human pathologies. The expression of pancreatic nitrotyrosine and its cellular source relative to insulitis were analysed in cases with increasing duration of type 1 diabetes and compared with non-diabetic autoantibody-negative and -positive cases. Pancreatic tail sections from non-diabetic autoantibody-negative cases (Group 1; n = 7), non-diabetic autoantibody-positive cases (Group 2; n = 6), recently diagnosed cases (Group 3; n = 6), 0...
February 2, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28154417/a-global-approach-for-quantitative-super-resolution-and-electron-microscopy-on-cryo-and-epoxy-sections-using-self-labeling-protein-tags
#19
Andreas Müller, Martin Neukam, Anna Ivanova, Anke Sönmez, Carla Münster, Susanne Kretschmar, Yannis Kalaidzidis, Thomas Kurth, Jean-Marc Verbavatz, Michele Solimena
Correlative light and electron microscopy (CLEM) is a powerful approach to investigate the molecular ultrastructure of labeled cell compartments. However, quantitative CLEM studies are rare, mainly due to small sample sizes and the sensitivity of fluorescent proteins to strong fixatives and contrasting reagents for EM. Here, we show that fusion of a self-labeling protein to insulin allows for the quantification of age-distinct insulin granule pools in pancreatic beta cells by a combination of super resolution and transmission electron microscopy on Tokuyasu cryosections...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28152182/reprogramming-of-pancreatic-acinar-cells-to-functional-beta-cells-by-in-vivo-transduction-of-a-polycistronic-construct-containing-pdx1-ngn3-mafa-in-mice
#20
C Cavelti-Weder, A Zumsteg, W Li, Q Zhou
To generate new beta cells after birth is a key focus of regenerative medicine, which could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: (1) the development of beta cells from putative precursor cells of the adult pancreas, which is termed neogenesis, (2) replication of existing beta cells, (3) differentiation from embryonic or induced pluripotent stem cells, and (4) reprogramming of non-beta cells to beta cells. Studies from the authors' laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA...
February 2, 2017: Current Protocols in Stem Cell Biology
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