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https://www.readbyqxmd.com/read/28097011/a-selective-gpr40-ffar1-agonist-ly2881835-provides-immediate-and-durable-glucose-control-in-rodent-models-of-type-2-diabetes
#1
Yanyun Chen, Min Song, Jonathan P Riley, Charlie C Hu, Xianbu Peng, Donalyn Scheuner, Krister Bokvist, Pranab Maiti, Steven D Kahl, Chahrzad Montrose-Rafizadeh, Chafiq Hamdouchi, Anne Reifel Miller
LY2881835 is a selective, potent, and efficacious GPR40 agonist. The objective of the studies described here was to examine the pharmacological properties of LY2881835 in preclinical models of T2D. Significant increases in insulin secretion were detected when LY2881835 was tested in primary islets from WT mice but not in islets from GPR40 KO mice. Furthermore, LY2881835 potentiated glucose stimulated insulin secretion in normal lean mice. Acute administration of LY2881835 lowered glucose during OGTTs in WT mice but not in GPR40 KO mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-egf-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#2
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a 3-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#3
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28093839/serum-undercarboxylated-osteocalcin-correlates-with-hemoglobin-a1c-in-children-with-recently-diagnosed-pediatric-diabetes
#4
Maria J Redondo, Beverly A Shirkey, Daniel W Fraga, A Osama Gaber, Omaima M Sabek
BACKGROUND: Osteocalcin (OC), a hormone secreted by osteoblasts, improves beta-cell function in vitro and in vivo. We aimed to understand the relationship between OC and hemoglobin A1c (HbA1c) in pediatric diabetes. METHODS: Children (n = 70; mean [SD] age = 11.8 years [3.1]; 34.3% non-Hispanic white, 46.3% Hispanic, 14.9% African-American, 4.5% other) newly diagnosed with diabetes (69.1% type 1 diabetes [T1D], 30.9% type 2 diabetes [T2D]) were studied...
January 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28092693/pathogenic-streptococcus-strains-employ-novel-escape-strategy-to-inhibit-bacteriostatic-effect-mediated-by-mammalian-peptidoglycan-recognition-protein
#5
Jing Wang, Youjun Feng, Changjun Wang, Swaminath Srinivas, Chen Chen, Hui Liao, Elaine He, Shibo Jiang, Jiaqi Tang
Pathogenic streptococcal species are responsible for some of the most lethal and prevalent animal and human infections. Previous reports have identified a candidate pathogenicity island (PAI) in two highly virulent clinical isolates of Streptococcus suis type 2 (SS2), a causative agent of high-mortality streptococcal toxic shock syndrome (STSS). This PAI contains a Type-IVC secretion system C subgroup (Type-IVC secretion system) that is involved in the secretion of unknown pathogenic effectors that are responsible for STSS caused by highly virulent strains of SS2...
January 16, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28091933/flagellar-regulation-and-virulence-in-the-entomopathogenic-bacteria-xenorhabdus-nematophila-and-photorhabdus-luminescens
#6
Alain Givaudan, Anne Lanois
There is a complex interplay between the regulation of flagellar motility and the expression of virulence factors in many bacterial pathogens. Here, we review the literature on the direct and indirect roles of flagellar motility in mediating the tripartite interaction between entomopathogenic bacteria (Photorhabdus and Xenorhabdus), their nematode hosts, and their insect targets. First, we describe the swimming and swarming motility of insect pathogenic bacteria and its impact on insect colonization. Then, we describe the coupling between the expression of flagellar and virulence genes and the dynamic of expression of the flagellar regulon during invertebrate infection...
December 28, 2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28091587/bacillus-volatiles-adversely-affect-the-physiology-and-ultra-structure-of-ralstonia-solanacearum-and-induce-systemic-resistance-in-tobacco-against-bacterial-wilt
#7
Hafiz Abdul Samad Tahir, Qin Gu, Huijun Wu, Yuedi Niu, Rong Huo, Xuewen Gao
Volatile organic compounds (VOCs) produced by various bacteria have significant potential to enhance plant growth and to control phytopathogens. Six of the most effective antagonistic Bacillus spp. were used in this study against Ralstonia solanacearum (Rsc) TBBS1, the causal agent of bacterial wilt disease in tobacco. Bacillus amyloliquefaciens FZB42 and Bacillus artrophaeus LSSC22 had the strongest inhibitory effect against Rsc. Thirteen VOCs produced by FZB42 and 10 by LSSC22 were identified using gas chromatography-mass spectrometry analysis...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088271/adamts-3-13-16-and-19-levels-in-patients-with-habitual-abortion
#8
Meryem Kuru Pekcan, Esma Sarıkaya, Aytekin Tokmak, Murat Alışık, Afra Alkan, Gülnur Özakşit, Özcan Erel
A disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs (ADAMTS) protein superfamily includes 19 secreted metalloproteases. Proteolytic substrates of ADAMTS enzymes have been linked to reproductive function. The aim of this study was to investigate serum ADAMTS-3, -13, -16, and -19 levels in women with habitual abortions compared with those in healthy controls. A total of 86 women were enrolled in this prospective case-control study. ADAMTS-3, -13, -16, and -19 values were recorded and analyzed in association with demographic and clinical parameters...
January 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28087885/absence-of-intestinal-microbiota-increases-%C3%A3-cyclodextrin-stimulated-reverse-cholesterol-transport
#9
Rima H Mistry, Henkjan J Verkade, Uwe J F Tietge
SCOPE: Non-digestible oligosaccharides are used as prebiotics for perceived health benefits, among these modulating lipid metabolism. However, the mechanisms of action are incompletely understood. The present study characterized the impact of dietary ß-cyclodextrin (ßCD, 10%, w/w), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional and also germ-free mice to establish dependency on metabolism by intestinal bacteria. METHODS AND RESULTS: In conventional ßCD-fed C57BL/6J wild-type mice plasma cholesterol decreased significantly (-40%, p<0...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#10
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28077642/studies-on-the-interaction-of-tumor-derived-hd5-alpha-defensins-with-adenoviruses-and-implications-for-oncolytic-adenovirus-therapy
#11
Charles Vragniau, Jens-Martin Hübner, Peter Beidler, Sucheol Gil, Kamola Saydaminova, Zhuo-Zhuang Lu, Roma Yumul, Hongjie Wang, Maximilian Richter, Pavel Sova, Charles Drescher, Pascal Fender, André Lieber
: Defensins are small anti-microbial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastro-intestinal and genito-urinary tracts. Here we demonstrate that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ, in patient biopsies. This finding triggered us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 virus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28075489/cough-augmentation-techniques-for-extubation-or-weaning-critically-ill-patients-from-mechanical-ventilation
#12
REVIEW
Louise Rose, Neill Kj Adhikari, David Leasa, Dean A Fergusson, Douglas McKim
BACKGROUND: There are various reasons why weaning and extubation failure occur, but ineffective cough and secretion retention can play a significant role. Cough augmentation techniques, such as lung volume recruitment or manually- and mechanically-assisted cough, are used to prevent and manage respiratory complications associated with chronic conditions, particularly neuromuscular disease, and may improve short- and long-term outcomes for people with acute respiratory failure. However, the role of cough augmentation to facilitate extubation and prevent post-extubation respiratory failure is unclear...
January 11, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28075049/src-homology-2-domain-containing-inositol-5-phosphatase-ameliorates-high-glucose-induced-extracellular-matrix-deposition-via-the-phosphatidylinositol-3-kinase-protein-kinase-b-pathway-in-renal-tubular-epithelial-cells
#13
Fan Li, Lisha Li, Jun Hao, Shuxia Liu, Huijun Duan
A typical hallmark of diabetic kidney disease (DKD) is an excessive deposition of extracellular matrix (ECM) in the glomerulus and renal tubulointerstitium, leading to glomerulosclerosis and tubular interstitial fibrosis. Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) is a negative regulator of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Here, we investigated the effect of SHIP on ECM deposition in diabetic mice and high glucose-stimulated human renal tubular epithelial cells (HK2 cells)...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28074109/improvement-of-quality-of-life-through-glycemic-control-by-liraglutide-a-glp-1-analog-in-insulin-naive-patients-with-type-2-diabetes-mellitus-the-page1-study
#14
Hitoshi Ishii, Tetsuji Niiya, Yasuhiro Ono, Naoyuki Inaba, Hideaki Jinnouchi, Hirotaka Watada
BACKGROUND: In addition to achieving good glycemic control, diabetes care management aims to improve the quality of life (QOL) in patients. Treatment-associated difficulties and side effects frequently cause deterioration in QOL. Liraglutide, a GLP-1 receptor agonist, is a novel injection drug that promotes insulin secretion. It is a user-friendly, once-daily injection with fewer hypoglycemic events. In this study, we aimed to examine the effect of liraglutide therapy on QOL in patients...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28069720/pregnancy-increases-the-renal-secretion-of-n1-methylnicotinamide-an-endogenous-probe-for-renal-cation-transporters-in-patients-prescribed-metformin
#15
Mackenzie C Bergagnini-Kolev, Mary F Hebert, Thomas R Easterling, Yvonne S Lin
N1-methylnicotinamide (1-NMN) has been investigated as an endogenous probe for the renal transporter activity of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 and 2-K (MATE1 and MATE2-K). As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1 and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected. Blood and urine samples collected from women prescribed metformin for type 2 diabetes, gestational diabetes and polycystic ovarian syndrome (PCOS) during early-, mid-, and late-pregnancy (n = 34 visits) and postpartum (n=14 visits) were analyzed for 1-NMN using liquid chromatography-mass spectrometry...
January 9, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28068879/electrospun-template-architecture-and-composition-regulate-neutrophil-netosis-in-vitro-and-in-vivo
#16
Allison E Fetz, Indira Neeli, Isaac A Rodriguez, Marko Z Radic, Gary Bowlin
Mounting evidence indicates that neutrophils, first responders to an implanted biomaterial, prime the microenvironment for recruited immune cells by secreting factors and releasing neutrophil extracellular traps (NETs) through NETosis. In this study, we investigated the role of electrospun template architecture and composition in regulating NETosis. Electrospun polydioxanone (PDO), collagen type I (COL), and blended PDO-COL templates (PC) were fabricated with small (0.25-0.35µm) and large (1.0-2.00µm) diameter fibers...
January 9, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28067918/structural-insights-into-the-secretin-translocation-channel-in-the-type-ii-secretion-system
#17
Zhaofeng Yan, Meng Yin, Dandan Xu, Yongqun Zhu, Xueming Li
The secretin GspD of the type II secretion system (T2SS) forms a channel across the outer membrane in Gram-negative bacteria to transport substrates from the periplasm to the extracellular milieu. The lack of an atomic-resolution structure of the GspD channel hinders the investigation of substrate translocation mechanism of T2SS. Here we report cryo-EM structures of two GspD channels (∼1 MDa), from Escherichia coli K12 and Vibrio cholerae, at ∼3 Å resolution. The structures reveal a pentadecameric channel architecture, wherein three rings of GspD N domains form the periplasmic channel...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28066685/linoleic-acid-is-a-diabetes-relevant-stimulator-of-retinal-inflammation-in-human-retinal-muller-cells-and-microvascular-endothelial-cells
#18
Megan E Capozzi, Gary W McCollum, David B Cousins, John S Penn
OBJECTIVE: To determine the effect of oleic acid and linoleic acid on the production and secretion of specific diabetic retinopathy- (DR-) related cytokines: vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and interleukin-8 (IL-8) by human retinal glial cells, retinal endothelial cells, and retinal pigment epithelial cells. These expression profiles will be compared to those obtained by treatment of the same cell types with elevated D-glucose, a diabetes-relevant stimulus often used in retinal cell culture experiments...
December 2016: Journal of Diabetes & Metabolism
https://www.readbyqxmd.com/read/28066137/betulin-suppressed-interleukin-1%C3%AE-induced-gene-expression-secretion-and-proteolytic-activity-of-matrix-metalloproteinase-in-cultured-articular-chondrocytes-and-production-of-matrix-metalloproteinase-in-the-knee-joint-of-rat
#19
Ho Jong Ra, Hyun Jae Lee, Ho Seung Jo, Dae Cheol Nam, Young Bok Lee, Byeong Hun Kang, Dong Kyu Moon, Dong Hee Kim, Choong Jae Lee, Sun-Chul Hwang
We investigated whether betulin affects the gene expression, secretion and proteolytic activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the rat knee joint to evaluate the potential chondroprotective effect of betulin. Rabbit articular chondrocytes were cultured and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1β (IL-1β)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28063169/progress-in-the-study-of-bioluminescent-earthworms
#20
Natalja S Rodionova, Emilia Rota, Aleksandra S Tsarkova, Valentin N Petushkov
Even though bioluminescent oligochaetes rarely catch people's eyes due to their secretive lifestyle, glowing earthworms sighting reports have come from different areas on all continents except Antarctica. A major breakthrough in the research of earthworm bioluminescence occurred in the 1960s with the studies of the North American Diplocardia longa. Comparative studies conducted on 13 earthworm species belonging to six genera showed that N-isovaleryl-3-aminopropanal (Diplocardia luciferin) is the common substrate for bioluminescence in all examined species, while luciferases appeared to be responsible for the color of bioluminescence...
January 7, 2017: Photochemistry and Photobiology
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