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macrophage and diabetes

Ashley R Burg, Hubert M Tse
Type 1 diabetes (T1D) is an autoimmune disease resulting in β-cell destruction mediated by islet-infiltrating leukocytes. The role of oxidative stress in human and murine models of T1D is highly significant as these noxious molecules contribute to diabetic complications and β-cell destruction, but their direct impact on dysregulated autoimmune responses is highly understudied. Pro-inflammatory macrophages play a vital role in the initiation and effector phases of T1D by producing reactive oxygen species and pro-inflammatory cytokines to facilitate β-cell destruction and by presenting antigen to autoreactive T cells...
October 17, 2017: Antioxidants & Redox Signaling
Dongmei Liu, Flor Elisa Morales, Heidi B IglayReger, Mary K Treutelaar, Amy E Rothberg, Monica J Hubal, Evan P Nadler, Jacques Robidoux, Hisham Barakat, Jeffrey F Horowitz, Eric P Hoffman, Charles F Burant, Paul M Gordon
Background Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance, however, the role of macrophage infiltration within skeletal muscle is still debateable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Methods Twenty-two non-diabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative RT-PCR), body composition (DXA) and insulin sensitivity (homeostatic model assessment and oral glucose tolerance test) were compared between groups and their associations were analyzed...
October 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Maria Vähätupa, Zuzet Martinez Cordova, Saara Aittomäki, Hannu Uusitalo, Tero A H Järvinen, Marko Pesu, Hannele Uusitalo-Järvinen
Diabetic retinopathy is a vision-threatening disease associated chronic retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a member of the proprotein convertase family of proteins, has been implicated in the regulation of angiogenesis due to its essential role in the activation of several angiogenic growth factors, including vascular endothelial growth factor-C (VEGF-C), VEGF-D and transforming growth factor - β (TGF- β). In the present study, we evaluated expression of furin in the retina and its role in retinal angiogenesis...
October 12, 2017: Experimental Eye Research
Nanthini Jayabalan, Soumyalekshmi Nair, Zarin Nuzhat, Gregory E Rice, Felipe A Zuñiga, Luis Sobrevia, Andrea Leiva, Carlos Sanhueza, Jaime Agustín Gutiérrez, Martha Lappas, Dilys Jane Freeman, Carlos Salomon
Obesity is an important public health issue worldwide, where it is commonly associated with the development of metabolic disorders, especially insulin resistance (IR). Maternal obesity is associated with an increased risk of pregnancy complications, especially gestational diabetes mellitus (GDM). Metabolism is a vital process for energy production and the maintenance of essential cellular functions. Excess energy storage is predominantly regulated by the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the body's major energy reservoir...
2017: Frontiers in Endocrinology
Karolline S da Silva, Paula R Pinto, Nelly T Fabre, Diego J Gomes, Karina Thieme, Ligia S Okuda, Rodrigo T Iborra, Vanessa G Freitas, Maria H M Shimizu, Walcy R Teodoro, Suely K N Marie, Tom Woods, Margaret A Brimble, Russell Pickford, Kerry-Anne Rye, Maristela Okamoto, Sergio Catanozi, Maria L Correa-Giannela, Ubiratan F Machado, Marisa Passarelli
Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization...
2017: Frontiers in Physiology
Corneliu Sima, Eduardo Montero, Daniel Nguyen, Marcelo Freire, Paul Norris, Charles N Serhan, Thomas E Van Dyke
Non-resolving inflammation is a central pathologic component of obesity, insulin resistance, type 2 diabetes and associated morbidities. The resultant hyperglycemia is deleterious to the normal function of many organs and its control significantly improves survival and quality of life for patients with diabetes. Macrophages play critical roles in both onset and progression of obesity-associated insulin resistance. Here we show that systemic activation of inflammation resolution prevents from morbid obesity and hyperglycemia under dietary overload conditions...
October 9, 2017: Scientific Reports
Dana M Previte, Jon D Piganelli
Previous work has indicated that Type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4+ T cell activation and differentiation. As CD4+ T cells are a significant contributor to pancreatic cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent advances: CD4+ T cells themselves generate ROS via NADPH oxidase expression and electron transport chain activity...
October 7, 2017: Antioxidants & Redox Signaling
Anaïs Szpigel, Isabelle Hainault, Aurélie Carlier, Nicolas Venteclef, Anne-Françoise Batto, Eric Hajduch, Catherine Bernard, Alain Ktorza, Jean-François Gautier, Pascal Ferré, Olivier Bourron, Fabienne Foufelle
AIMS/HYPOTHESIS: Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation...
October 7, 2017: Diabetologia
Seok-Beom Yong, Yoonsung Song, Yong-Hee Kim
Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity-induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6. TNF-α converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines...
December 2017: Biomaterials
Ping Hu, Nicholas H Hunt, Frank Arfuso, Lynn C Shaw, Mohammad Nasir Uddin, Meidong Zhu, Raj Devasahayam, Samuel J Adamson, Vicky L Benson, Tailoi Chan-Ling, Maria B Grant
Purpose: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. Methods: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels)...
October 1, 2017: Investigative Ophthalmology & Visual Science
Michael S Hu, Graham G Walmsley, Leandra A Barnes, Kipp Weiskopf, Robert C Rennert, Dominik Duscher, Michael Januszyk, Zeshaan N Maan, Wan Xing Hong, Alexander Tm Cheung, Tripp Leavitt, Clement D Marshall, Ryan C Ransom, Samir Malhotra, Alessandra L Moore, Jayakumar Rajadas, H Peter Lorenz, Irving L Weissman, Geoffrey C Gurtner, Michael T Longaker
The monocyte lineage is essential to normal wound healing. Macrophage inhibition or knockout in mice results in impaired wound healing through reduced neovascularization, granulation tissue formation, and reepithelialization. Numerous studies have either depleted macrophages or reduced their activity in the context of wound healing. Here, we demonstrate that by increasing the number of macrophages or monocytes in the wound site above physiologic levels via pullulan-collagen composite dermal hydrogel scaffold delivery, the rate of wound healing can be significantly accelerated in both wild-type and diabetic mice, with no adverse effect on the quality of repair...
October 5, 2017: JCI Insight
Tracey Gaspari, Iressa Spizzo, HongBin Liu, Yunshan Hu, Richard W Simpson, Robert E Widdop, Anthony E Dear
BACKGROUND: Sodium glucose transporter type 2 inhibitors may reduce cardiovascular events in type 2 diabetes. Our study aimed to determine the effect of the sodium glucose transporter type 2 inhibitor dapagliflozin on endothelial cell activation, vasoreactivity and atherogenesis using in vitro and in vivo models and identify associated molecular mechanisms. METHODS: In vitro studies utilised human vascular endothelial cells stimulated with tumour necrosis factor α or hyperglycaemic conditions...
October 1, 2017: Diabetes & Vascular Disease Research
Carolin Schliefsteiner, Birgit Hirschmugl, Susanne Kopp, Sanja Curcic, Eva Maria Bernhart, Gunther Marsche, Uwe Lang, Gernot Desoye, Christian Wadsack
Increased Lipoprotein associated phospholipase A2 (LpPLA2) has been associated with inflammatory pathologies, including Type 2 Diabetes. Studies on LpPLA2 and Gestational Diabetes Mellitus (GDM) are rare, and have focused mostly on maternal outcome. In the present study, we investigated whether LpPLA2 activity on foetal lipoproteins is altered by maternal GDM and/or obesity (a major risk factor for GDM), thereby contributing to changes in lipoprotein functionality. We identified HDL as the major carrier of LpPLA2 activity in the foetus, which is in contrast to adults...
October 3, 2017: Scientific Reports
Farida Hussan, Mohamad Fairuz Yahaya, Seong Lin Teoh, Srijit Das
The incidence of diabetes mellitus (DM) has increased globally. Various complications such as blindness, nephropathy leading to renal failure, neuropathy, foot ulceration, amputation, and disturbance in autonomic nervous system have been reported. Although, allopathy treatment still remains the treatment of choice, there is a need to look at the easy availability, patient compliance and cheaper cost of the drugs used in day-day practice. In this regard, complementary and alternative medicine has a greater role to play...
September 27, 2017: Mini Reviews in Medicinal Chemistry
Tine Van Bergen, Tjing-Tjing Hu, Isabelle Etienne, Geert E Reyns, Lieve Moons, Jean H M Feyen
The current standard of care in clinical practice for diabetic retinopathy (DR), anti-vascular endothelial growth factor (VEGF) therapy, has shown a significant improvement in visual acuity. However, treatment response can be variable and might be associated with potential side effects. This study was designed to investigate inhibition of placental growth factor (PlGF) as a possible alternative therapy for DR. The effect of the anti-PlGF antibody (PL5D11D4) was preclinically evaluated in various animal models by investigating different DR hallmarks, including inflammation, neurodegeneration, vascular leakage and fibrosis...
September 28, 2017: Experimental Eye Research
Huijeong Ahn, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Eui-Ju Hong, Beum-Soo An, Eunsong Lee, Geun-Shik Lee
Methylene blue (MB), which has antioxidant, anti-inflammatory, neuroprotective, and mitochondria protective effects, has been widely used as a dye and medication. However, the effect of MB on inflammasome activation has not yet been studied. Inflammasomes are multi-protein complexes that induce maturation of interleukins (ILs)-1β and -18 as well as caspase-1-mediated cell death, known as pyroptosis. Dysregulation of inflammasomes causes several diseases such as type 2 diabetes, Alzheimer's disease, and gout...
September 29, 2017: Scientific Reports
Jingfan Ma, Chang Guo, Yinlai Pan, Danyan Lin, Longxin Qiu, Longping Wen
Gynura formosana Kitam (family Compositae) has traditionally been used for the prevention of diabetes, cancer and inflammation in China. However, there are few reports of its anti-inflammatory effects. In the present study, after assessing the in vitro antioxidant activities of extracts from Gynura formosana Kitam leaves, the anti-inflammatory and antioxidant activities of ethyl acetate extract of Gynura formosana Kitam leaves (EAEG) were further investigated in rats using a cotton pellet-induced model of granuloma...
September 2017: Experimental and Therapeutic Medicine
Natsuko Saito, Shunsuke Kimura, Tomomi Miyamoto, Sanae Fukushima, Misato Amagasa, Yoshinori Shimamoto, Chieko Nishioka, Shiki Okamoto, Chitoku Toda, Kohei Washio, Atsushi Asano, Ichiro Miyoshi, Eiki Takahashi, Hiroshi Kitamura
We previously reported that ubiquitin-specific protease (USP) 2 in macrophages down-regulates genes associated with metabolic diseases, suggesting a putative anti-diabetic role for USP2 in macrophages. In this study, we evaluate this role at both cellular and individual levels. Isolated macrophages forcibly expressing Usp2a, a longer splicing variant of USP2, failed to modulate the insulin sensitivity of 3T3-L1 adipocytes. Similarly, macrophage-selective overexpression of Usp2a in mice (Usp2a transgenic mice) had a negligible effect on insulin sensitivity relative to wild type littermates following a three-month high-fat diet...
March 2017: Biochemistry and Biophysics Reports
Kahori Shimizu, Minako Okamoto, Tomoyuki Terada, Fuminori Sakurai, Hiroyuki Mizuguchi, Koji Tomita, Toru Nishinaka
Japanese patients with type 2 diabetes mellitus present a different responsiveness in terms of insulin secretion to glucose and body mass index (BMI) from other populations. The genetic background that predisposes Japanese individuals to type 2 diabetes mellitus is under study. Recent genetic studies demonstrated that the locus mapped in macrophage erythroblast attacher (MAEA) increases the susceptibility to type 2 diabetes mellitus in East Asians, including Japanese individuals. MAEA encodes a protein that plays a role in erythroblast enucleation and in the normal differentiation of erythroid cells and macrophages...
July 2017: Biochemistry and Biophysics Reports
Anbo Gao, Francisco S Cayabyab, Xi Chen, Jing Yang, Li Wang, Tianhong Peng, Yuncheng Lv
The present review provides a summary of recent evidence of sortilin expression, function, and regulation and its implications in lipid metabolism and development of lipid disorder diseases. As a member of the vacuolar protein sorting 10 protein (Vps10p) receptor family, sortilin mediates intracellular trafficking of diverse endogenous or exogenous protein substrates between the trans-Golgi network (TGN) and plasma membrane compartments. Recent studies reveal that sortilin regulates the expression of lipid genes, plasma lipid level, and the development of lipid disorder diseases...
September 25, 2017: DNA and Cell Biology
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