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Beta cell function

Xu Chen, Stefan Gustafsson, Thomas Whitington, Yan Borné, Erik Lorentzen, Jitong Sun, Peter Almgren, Jun Su, Robert Karlsson, Jie Song, Yi Lu, Yiqiang Zhan, Sara Hägg, Per Svensson, Karin E Smedby, Susan L Slager, Erik Ingelsson, Cecilia M Lindgren, Andrew P Morris, Olle Melander, Thomas Karlsson, Ulf de Faire, Kenneth Caidahl, Gunnar Engström, Lars Lind, Mikael C I Karlsson, Nancy L Pedersen, Johan Frostegård, Patrik K E Magnusson
Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWAS) in four European-ancestry cohorts, six SNPs in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta=0...
March 14, 2018: Human Molecular Genetics
Katarzyna Skrzypek, Yazmin Brito Barrera, Thomas Groth, Dimitrios Stamatialis
INTRODUCTION: Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability...
March 2018: International Journal of Artificial Organs
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Jason T C Lee, Iryna Shanina, Yung Ning Chu, Marc S Horwitz, James D Johnson
Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/w carbamazepine to achieve serum carbamazepine levels of 14...
March 15, 2018: Scientific Reports
Quan-Bo Zhang, Yu-Feng Qing, Cong-Cong Yin, Li Zhou, Xian-Shuang Liu, Qing-Sheng Mi, Jing-Guo Zhou
BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses and are implicated in several immune disorders including gouty arthritis. The expression of miR-146a is upregulated in the peripheral blood mononuclear cells of patients with inter-critical gout when compared to normouricemic and hyperuricemic controls and those patients with acute gout flares. However, the role of miR-146a in the development of gout remains unknown. Here, we used miR-146a knockout (KO) mice to test miR-146a function in a monosodium urate (MSU)-induced gouty arthritis model...
March 15, 2018: Arthritis Research & Therapy
Thanh D Do, Joseph F Ellis, Elizabeth K Neumann, Troy J Comi, Emily G Tillmaand, Ashley E Lenhart, Stanislav S Rubakhin, Jonathan Sweedler
The mammalian dorsal root ganglia (DRG) are located on the dorsal roots of the spinal nerves and contain cell bodies of primary sensory neurons. DRG cells have been classified into subpopulations based on their size, morphology, intracellular markers, response to stimuli, and neuropeptides. To understand the connections between DRG chemical heterogeneity and cellular function, we performed optically guided, high-throughput single cell profiling using sequential matrix-assisted laser desorption/ionization mass spectrometry (MS) to detect lipids, peptides, and several proteins in individual DRG cells...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, Philippe Lefebvre, Nadia Messaddeq, Quan Zhang, Catherine Dacquet, Luc Pénicaud, Stephan C Collins
The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo)...
2018: PloS One
Jiaqiang Ren, Dawn Ward, Steven Chen, Katherine Tran, Ping Jin, Marianna Sabatino, Pamela G Robey, David F Stroncek
BACKGROUND: Bone marrow stromal cells (BMSCs) have classically been cultured in media supplemented with fetal bovine serum (FBS). As an alternative to FBS, pooled solvent detergent apheresis platelets, HPGF-C18, was evaluated for BMSC culture. METHODS: A comparison of passage 2 BMSC growth revealed that 10% HPGF-C18 produced similar cell numbers as 20% FBS. Marrow aspirates from 5 healthy subjects were cultured for 4 passages in 10% HPGF-C18 or 20% FBS and were analyzed for proliferation, colony formation efficiency (CFE), surface marker expression, suppression of mixed lymphocyte reactions (MLRs), global gene and microRNA expression analysis...
March 14, 2018: Journal of Translational Medicine
Habtamu Wondifraw Baynes, Seifu Mideksa, Sintayehu Ambachew
Polyunsaturated Fatty acids have multiple effects in peripheral tissues and pancreatic beta cell function. The n-3 Polyunsaturated Fatty acids prevent and reverse high-fat-diet induced adipose tissue inflammation and insulin resistance. Insulin secretion is stimulated by glucose, amino acids, and glucagon- like peptide-1 in tissue containing high levels of n-3 Polyunsaturated Fatty acids than lower level of n-3 Polyunsaturated Fatty acids. Also, n-3 Polyunsaturated Fatty acids led to decreased production of prostaglandin, which in turn contributed to the elevation of insulin secretion...
March 14, 2018: Adipocyte
Xinlei Wang, Xiaoqin Zhao, Ranran Zhou, Yunjuan Gu, Xiaohui Zhu, Zhuqi Tang, Xinlu Yuan, Wei Chen, Rongping Zhang, Chen Qian, Shiwei Cui
AIMS/INTRODUCTION: Previous studies have shown that glucose peak time during oral glucose tolerance test varies in type 2 diabetes; however, characteristics of this heterogeneity remain unclear. This research aimed to investigate the characteristics of delayed glucose peak time in type 2 diabetes. METHODS: A total of 178 subjects who underwent oral glucose tolerance test were divided into five groups according to glucose peak time. RESULTS: Twenty-five subjects with normal glucose tolerance had a glucose peak at 30 min...
March 14, 2018: Journal of Diabetes Investigation
Wen-Ting K Tsai, Anna M Wu
The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell-surface targets in oncology and immunology. Protein engineering has been employed for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance...
March 14, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
Nilubon Singhto, Rattiyaporn Kanlaya, Angkhana Nilnumkhum, Visith Thongboonkerd
In kidney stone disease, macrophages secrete various mediators via classical secretory pathway and cause renal interstitial inflammation. However, whether their extracellular vesicles, particularly exosomes, are involved in kidney stone pathogenesis remained unknown. This study investigated alterations in exosomal proteome of U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) after exposure to calcium oxalate monohydrate (COM) crystals for 16-h using 2-DE-based proteomics approach. Six significantly altered proteins in COM-treated exosomes were successfully identified by nanoscale liquid chromatography-electrospray ionization-electron transfer dissociation tandem mass spectrometry as proteins involved mainly in immune processes, including T-cell activation and homeostasis, Fcγ receptor-mediated phagocytosis, interferon-γ (IFN-γ) regulation, and cell migration/movement...
2018: Frontiers in Immunology
Tetsuo Koshizuka, Takahiro Kobayashi, Ken Ishioka, Tatsuo Suzutani
Nedd4 is a family of ubiquitin E3 ligases that regulate numerous cellular processes. In this report, we showed that alpha- and beta-herpesviruses have membrane proteins that regulate the function of the Nedd4 family members. Although the homology search score was quite low, UL56 of herpes simplex virus type 1 and 2, ORF0 of varicella-zoster virus, UL42 of human cytomegalovirus, and U24 of human herpesvirus 6A, 6B, and 7 all possess at least one PPxY (PY) motif in their cytoplasmic domain, and are able to bind with Itch, a member of the Nedd4 family...
March 13, 2018: Scientific Reports
Anne-Marie Givel, Yann Kieffer, Alix Scholer-Dahirel, Philemon Sirven, Melissa Cardon, Floriane Pelon, Ilaria Magagna, Géraldine Gentric, Ana Costa, Claire Bonneau, Virginie Mieulet, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
High-grade serous ovarian cancers (HGSOC) have been subdivided into molecular subtypes. The mesenchymal HGSOC subgroup, defined by stromal-related gene signatures, is invariably associated with poor patient survival. We demonstrate that stroma exerts a key function in mesenchymal HGSOC. We highlight stromal heterogeneity in HGSOC by identifying four subsets of carcinoma-associated fibroblasts (CAF-S1-4). Mesenchymal HGSOC show high content in CAF-S1 fibroblasts, which exhibit immunosuppressive functions by increasing attraction, survival, and differentiation of CD25+ FOXP3+ T lymphocytes...
March 13, 2018: Nature Communications
Takahiko Niwa, Yasuo Yamakoshi, Hajime Yamazaki, Takeo Karakida, Risako Chiba, Jan C-C Hu, Takatoshi Nagano, Ryuji Yamamoto, James P Simmer, Henry C Margolis, Kazuhiro Gomi
Transforming growth factor-beta (TGF-β) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-β in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-β1 and TGF-β3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-β2 is high in dental pulp. TGF-β1 is a major isoform of TGF-β, and latent TGF-β1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11)...
March 13, 2018: Scientific Reports
Diane L McKay, Misha Eliasziw, C Y Oliver Chen, Jeffrey B Blumberg
Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans ( Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity...
March 11, 2018: Nutrients
Myungchul Song, Kyunghee Song, Sunghee Kim, Jinyoung Lee, Sueyun Hwang, Chingtack Han
Caenorhabditis elegans C09F5.1 is a nematode-specific gene that encodes a type II transmembrane protein containing the BRICHOS domain. The gene was isolated as a heat-sensitive mutant, but the function of the protein remained unclear. We examined the expression pattern and subcellular localization of C09F5.1 as well as its roles in thermotolerance and chaperone function. Expression of C09F5.1 under heat shock conditions was induced in a heat shock factor 1 (HSF-1)-dependent manner. However, under normal growth conditions, most cells types exposed to mechanical stimuli expressed C09F5...
March 13, 2018: Genes
Tom Podewin, Julia Ast, Johannes Broichhagen, Nicholas H F Fine, Daniela Nasteska, Philipp Leippe, Manuel Gailer, Teresa Buenaventura, Nisha Kanda, Ben J Jones, Celine M'Kadmi, Jean-Louis Baneres, Jacky Marie, Alejandra Tomas, Dirk Trauner, Anja Hoffmann-Röder, David J Hodson
Understanding the activation and internalization of G protein-coupled receptors (GPCRs) using conditional approaches is paramount to developing new therapeutic strategies. Here, we describe the design, synthesis, and testing of ExONatide , a benzylguanine-linked peptide agonist of the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR required for maintenance of glucose levels in humans. ExONatide covalently binds to SNAP-tagged GLP-1R-expressing cells, leading to prolonged cAMP generation, Ca2+ rises, and intracellular retention of the receptor...
February 28, 2018: ACS Central Science
Mirhane Hassan, Hala M Raslan, Hesham Gamal Eldin, Eman Mahmoud, Hanaa Alm-Elhuda Abd Elwajed
INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses. AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals. METHOD: Thirty T1D patients were included in the study...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Fang Fang, Bangxing Huang, Si Sun, Man Xiao, Jing Guo, Xiaoqing Yi, Jing Cai, Zehua Wang
High-risk human papillomavirus infection is essential for the malignant transformation of cervical cancer and can inhibit host miR-27a expression. We investigated the role and mechanism of miR-27a in cervical cancer progression. miR-27a is decreased in cervical cancer cell lines and miR-27a-agomir inhibited the cell proliferation, migration, and invasion properties of HeLa (adenocarcinoma) cells, but not in SiHa cells (squamous cell carcinoma). Luciferase assays revealed that miR-27a directly targets the 3'-UTR of transforming growth factor beta receptor I (TGF-βRI) and downregulates TGF-β signaling...
March 12, 2018: Cell Death & Disease
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