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lymphocytes and diabetes type 2

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https://www.readbyqxmd.com/read/28992267/white-blood-cell-fractions-correlate-with-lesions-of-diabetic-kidney-disease-and-predict-loss-of-kidney-function-in-type-2-diabetes
#1
Kevin M Wheelock, Pierre-Jean Saulnier, Stephanie K Tanamas, Pavithra Vijayakumar, E Jennifer Weil, Helen C Looker, Robert L Hanson, Kevin V Lemley, Berne Yee, William C Knowler, Samy Hadjadj, Bezhad Najafian, Michael Mauer, Robert G Nelson
Background: Inflammation linked to diabetic kidney disease (DKD) may affect white blood cell (WBC) counts and differentials. We examined the cross-sectional associations of total WBC count and WBC fractions with structural lesions of DKD in 108 Pima Indians with Type 2 diabetes who underwent research kidney biopsies. We also examined the longitudinal association of these WBC variables with renal function loss (RFL) in 941 Europeans with Type 2 diabetes from the SURDIAGENE study. Methods: Associations of WBC variables with morphometric parameters were assessed by linear regression...
July 18, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28988715/self-transducible-bimodal-pdx1-foxp3-protein-lifts-insulin-secretion-and-curbs-autoimmunity-boosting-tregs-in-type-1-diabetic-mice
#2
Christina Amatya, Ilian A Radichev, Jacob Ellefson, Mark Williams, Alexei Y Savinov
Type 1 diabetes (T1D) is characterized by massive destruction of insulin-producing β cells by autoreactive T lymphocytes, arising via defective immune tolerance. Therefore, effective anti-T1D therapeutics should combine autoimmunity-preventing and insulin production-restoring properties. We constructed a cell-permeable PDX1-FOXP3-TAT fusion protein (FP) composed of two transcription factors: forkhead box P3 (FOXP3), the master regulator of differentiation and functioning of self-tolerance-promoting Tregs, and pancreatic duodenal homeobox-1 (PDX1), the crucial factor supporting β cell development and maintenance...
September 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28986401/activation-of-cd4-and-cd8-t-lymphocytes-by-insulin-and-gad-in-patients-with-type-1-or-2-diabetes-mellitus
#3
Borros M Arneth
BACKGROUND: The origin of autoimmune disease type 1 diabetes is still unknown. AIM: This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers. MATERIALS AND METHODS: The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD...
October 6, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28983603/inflammatory-and-oxidative-stress%C3%A2-associated-factors-in-chronic-intermittent-hypoxia-in-chinese-patients-rats-lymphocytes-and-endotheliocytes
#4
Hui Ren, Ke Hu
In order to investigate the association between inflammatory and oxidative stress (OS)‑associated factors in chronic intermittent hypoxia (CIH), 238 CIH patients and 156 healthy volunteers were included. CIH rat and lymphocytes were used as experimental models. Interleukin (IL)‑6, tumor necrosis factor‑α (TNF‑α), C‑reactive protein (CRP), nitric oxide (NO) and nitric oxide synthase (NOS) were analyzed. Patients with CIH were older, with hypertension, increased heart rate (HR) and body mass index (BMI), and there were more males than females...
September 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28977608/anti-tcr%C3%AE-mab-in-combination-with-neurogenin3-gene-therapy-reverses-established-overt-type-1-diabetes-in-female-nod-mice
#5
Aini Xie, Rongying Li, Tao Jiang, Hui Yan, Hedong Zhang, Yisheng Yang, Lina Yang, Vijay Yechoor, Lawrence Chan, Wenhao Chen
Insulin-producing β cells in patients with type 1 diabetes (T1D) are destroyed by T lymphocytes. We investigated whether targeting the T-cell receptor (TCR) with a monoclonal antibody (mAb) abrogates T-cell response against residual and newly formed islets in overtly diabetic nonobese diabetic (NOD) mice. NOD mice with blood glucose levels of 250 to 350 mg/dL or 350 to 450 mg/dL were considered as new-onset or established overt diabetes, respectively. These diabetic NOD mice were transiently treated with an anti-TCR β chain (TCRβ) mAb, H57-597, for 5 days...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28883439/t-cells-display-mitochondria-hyperpolarization-in-human-type-1-diabetes
#6
Jing Chen, Anna V Chernatynskaya, Jian-Wei Li, Matthew R Kimbrell, Richard J Cassidy, Daniel J Perry, Andrew B Muir, Mark A Atkinson, Todd M Brusko, Clayton E Mathews
T lymphocytes constitute a major effector cell population in autoimmune type 1 diabetes. Despite essential functions of mitochondria in regulating activation, proliferation, and apoptosis of T cells, little is known regarding T cell metabolism in the progression of human type 1 diabetes. In this study, we report, using two independent cohorts, that T cells from patients with type 1 diabetes exhibited mitochondrial inner-membrane hyperpolarization (MHP). Increased MHP was a general phenotype observed in T cell subsets irrespective of prior antigen exposure, and was not correlated with HbA1C levels, subject age, or duration of diabetes...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843649/change-in-nomenclature-for-the-immunologic-synapse-from-troxis-necrosis-to-trogocytosis
#7
Samuel W French
The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the CD4 lymphocyte...
August 24, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28783703/lag3-limits-regulatory-t-cell-proliferation-and-function-in-autoimmune-diabetes
#8
Qianxia Zhang, Maria Chikina, Andrea L Szymczak-Workman, William Horne, Jay K Kolls, Kate M Vignali, Daniel Normolle, Maria Bettini, Creg J Workman, Dario A A Vignali
Inhibitory receptors (IRs) are pivotal in controlling T cell homeostasis because of their intrinsic regulation of conventional effector T (Tconv) cell proliferation, viability, and function. However, the role of IRs on regulatory T cells (Tregs) remains obscure because they could be required for suppressive activity and/or limit Treg function. We evaluated the role of lymphocyte activation gene 3 (LAG3; CD223) on Tregs by generating mice in which LAG3 is absent on the cell surface of Tregs in a murine model of type 1 diabetes...
March 31, 2017: Science Immunology
https://www.readbyqxmd.com/read/28769554/the-modulation-of-enzyme-indoleamine-2-3-dioxygenase-from-dendritic-cells-for-the-treatment-of-type-1-diabetes-mellitus
#9
REVIEW
Débora Moitinho Abram, Luis Gustavo Romani Fernandes, Antônio Celso Saragossa Ramos Filho, Patrícia Ucelli Simioni
Diabetes mellitus type 1 (DM1) is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28765956/anti-cd20-monoclonal-antibody-combined-with-adenovirus-vector-mediated-il-10-regulates-spleen-cd4-cd8-t%C3%A2-cells-and-t-bet-gata-3-expression-in-nod-mice
#10
Aiping Tang, Cheng Li, Zhihong Chen, Tang Li
Type 1 diabetes (T1D) is an autoimmune disease characterized by a selective destruction of insulin-secreting β-cells. Both T cells and B cells serve a crucial role in pathogenesis and development of T1D. CD20 is a specific membrane antigen of B lymphocytes, while interleukin (IL)‑10 is an important cytokine secreted by T helper 2 cells and has a short half‑life in vivo. The combined effect of anti‑CD20 and IL‑10 on immune function of mice with T1D remains unknown. In the present study, 30 non‑obese diabetic (NOD) mice were treated with anti‑CD20 and adenoviral vector‑mediated interleukin‑10 (Ad‑mIL‑10) therapy...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28734574/early-reduction-of-matrix-metalloproteinase-8-serum-levels-is-associated-with-leptin-drop-and-predicts-diabetes-remission-after-bariatric-surgery
#11
Luca Liberale, Aldo Bonaventura, Federico Carbone, Maria Bertolotto, Paola Contini, Nicola Scopinaro, Giovanni Bruno Camerini, Francesco Saverio Papadia, Renzo Cordera, Giovanni Guido Camici, Franco Dallegri, Gian Franco Adami, Fabrizio Montecucco
BACKGROUND: We aimed at investigating whether the acute abrogation of leptin after bariatric surgery is able to reduce neutrophil activation and potentially affect type 2 diabetes mellitus (T2DM) remission. METHODS: Metabolic and inflammatory parameters (i.e. leptin, IL-6 and neutrophil products) were compared at baseline (before bariatric surgery), one month, one and three years after surgery in morbid obese (MOB) T2DM patients (n=12) and non-MOB controls (n=32)...
July 13, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#12
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
August 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28690850/agammaglobulinaemia-despite-terminal-b-cell-differentiation-in-a-patient-with-a-novel-lrba-mutation
#13
Nashat Al Sukaiti, Khwater AbdelRahman, Jalila AlShekaili, Sumaya Al Oraimi, Aisha Al Sinani, Nasser Al Rahbi, Vicky Cho, Matt Field, Matthew C Cook
Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstitial lung disease. The patient was treated with CTLA4-Ig (abatacept) with good outcome every 2 weeks for a period of 3 months...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28582723/neutrophil-to-lymphocyte-ratio-is-associated-with-diabetic-peripheral-neuropathy-in-type-2-diabetes-patients
#14
Siying Liu, Hangping Zheng, Xiaoming Zhu, Fei Mao, Shuo Zhang, Hongli Shi, Yiming Li, Bin Lu
OBJECTIVE: Diabetic peripheral neuropathy (DPN) had been demonstrated as a chronic inflammation state and one of the most common complications of type 2 diabetes mellitus (T2DM). Neutrophil-to-lymphocyte ratio (NLR) is a novel marker to reflect many kinds of chronic inflammation disease including diabetes. We aim to evaluate the association between NLR and DPN and to determine whether NLR could be a new indicator of DPN in type 2 diabetes patients. METHODS: We retrospect the consecutive medical files of T2DM patients...
May 12, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28553592/study-of-neutrophil-lymphocyte-ratio-as-novel-marker-for-diabetic-nephropathy-in-type-2-diabetes
#15
Sagar Ashokrao Khandare, Sachin Chittawar, Nitin Nahar, T N Dubey, Zahraan Qureshi
INTRODUCTION: Diabetic nephropathy (DN) is a microvascular complication of diabetes. DN is clinically manifested as an increase in urine albumin excretion. Total white blood cell count is a crude but sensitive indicator of inflammation and studied in many cardiac and noncardiac diseases as an inflammatory marker such as acute myocardial infarction, stroke, and heart failure. In this study, the association of neutrophil-lymphocyte ratio (NLR) with DN is studied. PATIENTS AND METHODS: It is an observational cross-sectional study...
May 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28496193/exendin-4-exhibits-enhanced-anti-tumor-effects-in-diabetic-mice
#16
Lan He, Priscilla T Y Law, Chun Kwok Wong, Juliana C N Chan, Paul K S Chan
Type 2 diabetes (T2D) is associated with increased risk of cancers. In this connection, we previously demonstrated the promoting effect of diabetes on HPV-associated carcinogenesis using a xenograft model in db/db diabetic mice. The underlying mechanism of this observation might be partly contributed by dysregulated immune response in diabetes. In this study, we hypothesized that the impaired anti-tumor immune response in diabetic status could be modulated by exendin-4, a glucagon-like protein receptor agonist which exhibits anti-diabetic effects...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28491871/the-imbalance-of-b-lymphocyte-subsets-in-subjects-with-different-glucose-tolerance-relationship-with-metabolic-parameter-and-disease-status
#17
Chao Deng, Yufei Xiang, Tingting Tan, Zhihui Ren, Chuqing Cao, Bingwen Liu, Gan Huang, Xiangbing Wang, Zhiguang Zhou
B lymphocytes are involved in inflammation and are related to insulin resistance in obesity and type 2 diabetes (T2D). This study investigated the phenotype and frequency of B-lymphocyte subsets in subjects recently diagnosed with T2D (n = 60), impaired glucose regulation (IGR, n = 73), and normal glucose tolerance (NGT, n = 169) by flow cytometry. T2D subjects had an increased percentage of CD19(+)CD23(+) (B-2) cells and a decreased percentage of CD19(+)CD23(-) (B-1) cells attributing to CD19(+)CD23(-)CD5(-) (B-1b) cells, but not CD19(+)CD23(-)CD5(+) (B-1a) cells, compared to NGT and IGR subjects...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28491063/isa-2011b-a-phosphatidylinositol-4-phosphate-5-kinase-%C3%AE-inhibitor-impairs-cd28-dependent-costimulatory-and-pro-inflammatory-signals-in-human-t-lymphocytes
#18
Martina Kunkl, Nicla Porciello, Marta Mastrogiovanni, Cristina Capuano, Federica Lucantoni, Chiara Moretti, Jenny L Persson, Ricciarda Galandrini, Raffaella Buzzetti, Loretta Tuosto
Phosphatidylinositol 4,5-biphosphate (PIP2) is a membrane phospholipid that controls the activity of several proteins regulating cytoskeleton reorganization, cytokine gene expression, T cell survival, proliferation, and differentiation. Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) are the main enzymes involved in PIP2 biosynthesis by phosphorylating phosphatidylinositol 4-monophosphate (PI4P) at the D5 position of the inositol ring. In human T lymphocytes, we recently found that CD28 costimulatory molecule is pivotal for PIP2 turnover by recruiting and activating PIP5Kα...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28461573/genetic-and-small-molecule-disruption-of-the-aid-rad51-axis-similarly-protects-nonobese-diabetic-mice-from-type-1-diabetes-through-expansion-of-regulatory-b-lymphocytes
#19
Jeremy J Ratiu, Jeremy J Racine, Muneer G Hasham, Qiming Wang, Jane A Branca, Harold D Chapman, Jing Zhu, Nina Donghia, Vivek Philip, William H Schott, Clive Wasserfall, Mark A Atkinson, Kevin D Mills, Caroline M Leeth, David V Serreze
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte-targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte-directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28450222/probiotic-treatment-protects-against-the-pro-depressant-like-effect-of-high-fat-diet-in-flinders-sensitive-line-rats
#20
Anders Abildgaard, Betina Elfving, Marianne Hokland, Sten Lund, Gregers Wegener
Major depressive disorder (MDD) is highly associated with dysmetabolic conditions, such as obesity and diabetes mellitus type 2, and the gut microbiota may interact with both disease entities. We have previously shown that a high-fat diet (HFD) exacerbated depressive-like behaviour uniquely in Flinders Sensitive Line (FSL) rats that inherently present with an increased level of depressive-like behaviour compared with Flinders Resistant Line (FRL) rats. We therefore investigated whether multispecies probiotics possessed anti-depressant-like effect in FSL rats or protected against the pro-depressant-like effect of HFD...
April 25, 2017: Brain, Behavior, and Immunity
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