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Insulin antibodies

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https://www.readbyqxmd.com/read/28938451/antibody-mediated-targeting-of-the-fgfr1c-isoform-increases-glucose-uptake-in-white-and-brown-adipose-tissue-in-male-mice
#1
Jo E Lewis, Ricardo J Samms, Scott Cooper, Jeni C Luckett, Alan C Perkins, James D Dunbar, Dennis P Smith, Paul J Emmerson, Andrew C Adams, Francis J P Ebling, Kostas Tsintzas
The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycaemia and protect from diet- and genetically-induced obesity in rodents and non-human primates. However, it is currently unknown which tissue(s) contribute to this glucose lowering effect...
August 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935478/development-and-validation-of-a-cell-based-assay-for-the-detection-of-neutralizing-antibodies-against-recombinant-insulins
#2
Sanjukta Chatterjee, Laxmikant Vashishta, Vinit S Waichale, Vivek G Nayak, Ramakrishnan Melarkode, Charles M Donnelly, Patrick T Vallano, Narendra Chirmule, Nilanjan Sengupta
Recombinant biopharmaceuticals can induce generation of anti-drug antibodies, which could potentially neutralize therapeutic drug activity. In this report, we describe development and validation of a cell-based assay for detection of neutralizing antibodies (Nab) against insulin and insulin analogues. In order to achieve clinically meaningful sensitivity the method used an early signalling event, insulin induced insulin receptor phosphorylation as the endpoint. Percentage insulin receptor phosphorylation in cell lysates was measured using ECL based ELISA...
September 18, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28935176/current-insight-in-the-localized-insulin-derived-amyloidosis-lida-clinico-pathological-characteristics-and-differential-diagnosis
#3
REVIEW
Amir Mehdi Ansari, Lais Osmani, Aerielle E Matsangos, Qing K Li
BACKGROUND: In diabetic patients, subcutaneous insulin injection may cause several types of injection site-related lesions, such as lipoatrophy, insulin-induced cutaneous lipohypertrophy (IICL), allergic reaction, and iatrogenic localized insulin-derived amyloidosis (LIDA). Among these complications, both IICL and LIDA present as tumor-like and slow growing lesions; and they may be confused with one another. The clinical implication and management of IICL and LIDA are different. LIDA causes poor blood glycemic controls due to inadequate absorption of the insulin...
September 1, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28934434/high-sensitivity-assays-for-plasmodium-falciparum-infection-by-immuno-polymerase-chain-reaction-detection-of-pfideh-and-pfldh-antigens
#4
Jianbing Mu, John F Andersen, Jesus G Valenzuela, Thomas E Wellems
Background: Rapid diagnostic tests based on Plasmodium falciparum histidine-rich protein II (PfHRP-II) and P. falciparum lactate dehydrogenase (PfLDH) antigens are widely deployed for detection of P. falciparum infection; however, these tests often miss cases of low-level parasitemia, and PfHRP-II tests can give false-negative results when P. falciparum strains do not express this antigen. Methods: We screened proteomic data for highly expressed P. falciparum proteins and compared their features to those of PfHRP-II and PfLDH biomarkers...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28928405/nanopore-extended-field-effect-transistor-for-selective-single-molecule-biosensing
#5
Ren Ren, Yanjun Zhang, Binoy Paulose Nadappuram, Bernice Akpinar, David Klenerman, Aleksandar P Ivanov, Joshua B Edel, Yuri Korchev
There has been a significant drive to deliver nanotechnological solutions to biosensing, yet there remains an unmet need in the development of biosensors that are affordable, integrated, fast, capable of multiplexed detection, and offer high selectivity for trace analyte detection in biological fluids. Herein, some of these challenges are addressed by designing a new class of nanoscale sensors dubbed nanopore extended field-effect transistor (nexFET) that combine the advantages of nanopore single-molecule sensing, field-effect transistors, and recognition chemistry...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927270/proteomic-analysis-of-peripheral-blood-mononuclear-cells-pbmc-after-a-high-fat-high-carbohydrate-meal-with-orange-juice
#6
Daniela F Seixas Chaves, Paulo C Carvalho, Elisa Brasili, Marcelo Macedo Rogero, Neuza Mariko Aymoto Hassimotto, Jolene K Diedrich, James J Moresco, John R Yates, Franco Maria Lajolo
Oxidative stress and inflammation play a role in the physiopathology of insulin resistance, diabetes and cardiovascular disease. A single high-fat, high-carbohydrate (HFHC) meal induces an increase in inflammatory and oxidative stress markers in peripheral blood mononuclear cells (PBMC). Previous studies have shown that orange juice is able to prevent this response by inhibiting toll like receptors (TLR) expression and endotoxemia. Our goal was to study the proteome response in PBMC after the consumption of a HFHC meal consumed with water, orange juice or an isocaloric beverage (water with glucose)...
September 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28923650/does-renal-tubular-injury-induced-local-tissue-hypoxia-involve-post-transplantation-erythrocytosis
#7
A Unal, S Ata, C Karakurkcu, M Z Ciraci, I Kocyigit, M H Sipahioglu, B Tokgoz, O Oymak
BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923480/impact-of-morphine-on-the-expression-of-insulin-receptor-and-protein-levels-of-insulin-igfs-in-rat-neural-stem-cells
#8
Sadegh Salarinasab, AliReza Nourazarian, Masoud Nikanfar, Nima Abdyazdani, Masoumeh Kazemi, Navid Feizy, Reza Rahbarghazi
Alzheimer's disease is correlated with neuronal degeneration and loss of neuronal precursors in different parts of the brain. It has been found disturbance in the homeostasis neural stem cells (NSCs) can cause neurodegeneration. Morphine, an analgesic agent, can disrupt the dynamic and normal state of NSCs. However, more investigations are required to clearly address underlying mechanisms. The current experiment aimed to investigate the effects of morphine on the cell distribution of insulin factor and receptor and insulin-like growth factors (IGF1, IGF2) in NSCs...
September 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#9
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912863/a-novel-mutation-in-the-hepatocyte-nuclear-factor-1%C3%AE-gene-in-maturity-onset-diabetes-of-the-young-5-with-multiple-renal-cysts-and-pancreas-hypogenesis-a-case-report
#10
You Lv, Zhuo Li, Kan He, Ying Gao, Xianchao Xiao, Yujia Liu, Guixia Wang
A 17-year-old Chinese male was hospitalized exhibiting hyperglycemia and increased serum urea nitrogen and creatinine levels in addition to weight loss. The patient was treated with gliclazide. The patient was 150 cm tall, weighed 35 kg and had no family history of diabetes or kidney disease. Physical examination revealed cephalus quadratus, rachitic rosary and a visible toe-out gait. Laboratory examinations revealed that the patient's fasting plasma glucose and glycosylated hemoglobin levels were markedly increased, fasting plasma C-peptide level was slightly increased and no peak 2 h postprandial was observed...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28903937/ectopic-fatty-acid-binding-protein-4-expression-in-the-vascular-endothelium-is-involved-in-neointima-formation-after-vascular-injury
#11
Takahiro Fuseya, Masato Furuhashi, Megumi Matsumoto, Yuki Watanabe, Kyoko Hoshina, Tomohiro Mita, Shutaro Ishimura, Marenao Tanaka, Tetsuji Miura
BACKGROUND: Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes, macrophages, and endothelial cells of capillaries but not arteries. FABP4 is secreted from adipocytes in association with lipolysis, and an elevated circulating FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the link between FABP4 and endovascular injury. We investigated the involvement of ectopic FABP4 expression in endothelial cells in neointima hyperplasia after vascular injury...
September 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28894445/adipose-tissue-inflammation-induces-b-cell-inflammation-and-decreases-b-cell-function-in-aging
#12
REVIEW
Daniela Frasca, Bonnie B Blomberg
Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28889965/losartan-counteracts-the-effects-of-cardiomyocyte-swelling-on-glucose-uptake-and-insulin-receptor-substrate-1-levels
#13
Yamil Gerena, Janice Griselle Lozada, Bryan Jael Collazo, Jarold Méndez-Álvarez, Jennifer Méndez-Estrada, Walmor C De Mello
A growing body of evidence demonstrates an association between Angiotensin II (Ang II) receptor blockers (ARBs) and enhanced glucose metabolism during ischemic heart disease. Despite these encouraging results, the mechanisms responsible for these effects during ischemia remain poorly understood. In this study we investigated the influence of losartan, an AT1 receptor blocker, and secreted Ang II (sAng II) on glucose uptake and insulin receptor substrate (IRS-1) levels during cardiomyocyte swelling. H9c2 cells were differentiated to cardiac muscle and the levels of myogenin, Myosin Light Chain (MLC), and membrane AT1 receptors were measured using flow cytometry...
September 7, 2017: Peptides
https://www.readbyqxmd.com/read/28880481/%C3%AE-cells-are-not-uniform-after-all-novel-insights-into-molecular-heterogeneity-of-insulin-secreting-cells
#14
REVIEW
Dana Avrahami, Yue J Wang, Agnes Klochendler, Yuval Dor, Benjamin Glaser, Klaus H Kaestner
While the β-cells of the endocrine pancreas are defined as cells with high levels of insulin production and tight stimulus-secretion coupling, the existence of functional heterogeneity among them has been known for decades. Recent advances in molecular technologies, in particular single-cell profiling on both the protein and messenger RNA level, have uncovered that β-cells exist in several antigenically and molecularly definable states. Using antibodies to cell surface markers or multidimensional clustering of β-cells using more than 20 protein markers by mass cytometry, 4 distinct groups of β-cells could be differentiated...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28864187/quantum-dot-nanoprobes-and-aotf-based-cross-talk-eliminated-six-color-imaging-of-biomolecules-in-cellular-system
#15
Solji Park, Parthasarathy Arumugam, Baskaran Purushothaman, Sung-Yon Kim, Dal-Hee Min, Noo Li Jeon, Joon Myong Song
Primary cell cultures mimic the physiology and genetic makeup of in-vivo tissue of origin, nonetheless, a complication in the derivation and propagation of primary cell culture limits its use in biological research. However, in-vitro models using primary cells might be a complement model to mimic in vivo response. But, conventional techniques such as western blot and PCR employed to study the expression and activation of proteins requires a large number of cells, hence repeated establishment and maintenance of primary culture are unavoidable...
September 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28854965/adipose-stem-cells-from-chronic-pancreatitis-patients-improve-mouse-and-human-islet-survival-and-function
#16
Lili Song, Zhen Sun, Do-Sung Kim, Wenyu Gou, Charlie Strange, Huansheng Dong, Wanxing Cui, Gary Gilkeson, Katherine A Morgan, David B Adams, Hongjun Wang
BACKGROUND: Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation...
August 30, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28846865/insulin-glargine-and-its-two-active-metabolites-a-sensitive-16pm-and-robust-simultaneous-hybrid-assay-coupling-immunoaffinity-purification-with-lc-ms-ms-to-support-biosimilar-clinical-studies
#17
Yang Xu, Li Sun, Melanie Anderson, Philippe Bélanger, Vincent Trinh, Patricia Lavallée, Bhavna Kantesaria, Marie-Josée Marcoux, Sheila Breidinger, Kevin P Bateman, Dina Goykhman, Eric J Woolf
MK-1293 is a newly approved follow-on/biosimilar insulin glargine for the treatment of Type 1 and Type 2 diabetics. To support pivotal clinical studies during biosimilar evaluation, a sensitive, specific and robust liquid chromatography and tandem mass spectrometry (LC-MS/MS) assay for the simultaneous quantification of glargine and its two active metabolites, M1 and M2 were developed. Strategies to overcome analytical challenges, so as to optimize assay sensitivity and improve ruggedness, were evolved, resulting in a fully validated LC-MS/MS method with a lower limit of quantification (LLOQ) at 0...
August 19, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28844948/inhibition-of-insulin-pi3k-akt-signaling-decreases-adipose-sortilin-1-in-mice-and-3t3-l1-adipocytes
#18
Jibiao Li, Cheng Chen, Yuan Li, David J Matye, Yifeng Wang, Wen-Xing Ding, Tiangang Li
Sortilin 1(Sort1) is a vesicle trafficking receptor that mediates protein sorting in the endocytic and exocytic pathways. Sort1 is a component of the GLUT4 storage vesicles in adipocytes and is also involved in the regulation of adipogenesis. Sort1 protein is reduced in adipose of obese mice and humans, but the underlying cause is not fully understood. Here we report that insulin/PI3K/AKT signaling cascade critically regulates adipose Sort1 protein abundance. Administration of a PI3K inhibitor rapidly decreased Sort1 protein but not mRNA in adipose of chow-fed mice...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28843667/the-specific-localization-of-advanced-glycation-end-products-ages-in-rat-pancreatic-islets
#19
Yuta Morioka, Kiyoshi Teshigawara, Yasuko Tomono, Dengli Wang, Yasuhisa Izushi, Hidenori Wake, Keyue Liu, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori
Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28842400/increased-effector-memory-insulin-specific-cd4-t-cells-correlate-with-insulin-autoantibodies-in-recent-onset-type-1-diabetic-patients
#20
Justin A Spanier, Nathanael L Sahli, Joseph C Wilson, Tijana Martinov, Thamotharampillai Dileepan, Adam L Burrack, Erik B Finger, Bruce R Blazar, Aaron W Michels, Antoinette Moran, Marc K Jenkins, Brian T Fife
Type 1 diabetes (T1D) results from T-cell mediated destruction of insulin producing beta cells. Insulin represents a key self-antigen in disease pathogenesis as recent studies identified proinsulin responding T-cells from inflamed pancreatic islets of recent onset T1D organ donors. These cells respond to an insulin B chain epitope presented by human leukocyte antigen (HLA) DQ8 molecule associated with high T1D risk. It is now critical to understand insulin specific T-cell frequency and phenotype in peripheral blood...
August 25, 2017: Diabetes
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