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macrophage and diabetes

Bin Shen, Yu Zhang, Wei Dai, Yupo Ma, Yongping Jiang
BACKGROUND: Hematopoietic CD34(+) stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how Sall4B might affect the expansion of CD34(+) cells derived from nonhuman primates. METHODS: Sall4B was overexpressed in nonhuman primate bone marrow-derived CD34(+) cells via a lentiviral transduction system...
October 20, 2016: Stem Cell Research & Therapy
Hosana G Rodrigues, Marco A R Vinolo, Fabio T Sato, Juliana Magdalon, Carolina M C Kuhl, Ana S Yamagata, Ana Flávia M Pessoa, Gabriella Malheiros, Marinilce F Dos Santos, Camila Lima, Sandra H Farsky, Niels O S Camara, Maria R Williner, Claudio A Bernal, Philip C Calder, Rui Curi
INTRODUCTION: Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. OBJECTIVES: We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. METHODS: Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0...
2016: PloS One
Zhong'e Zhou, Yong Tang, Xian Jin, Chengjun Chen, Yi Lu, Liang Liu, Chengxing Shen
Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects...
2016: Journal of Diabetes Research
Ross M Clark, Brittany Coffman, Paul G McGuire, Thomas R Howdieshell
BACKGROUND: Murine models of diabetes and obesity have provided insight into the pathogenesis of impaired epithelialization of excisional skin wounds. However, knowledge of postischemic myocutaneous revascularization in these models is limited. MATERIALS AND METHODS: A myocutaneous flap was created on the dorsum of wild type (C57BL/6), genetically obese and diabetic (ob/ob, db/db), complementary heterozygous (ob(+)/ob(-), db(+)/db(-)), and diet-induced obese (DIO) mice (n=48 total; five operative mice per strain and three unoperated mice per strain as controls)...
2016: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
PURPOSE OF REVIEW: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments. RECENT FINDINGS: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-1 are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance...
October 13, 2016: Current Opinion in Allergy and Clinical Immunology
Huiting Su, Ning Na, Xiaodong Zhang, Yong Zhao
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins...
October 17, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
S A Yuca, E A Cimbek, Y Şen, O Güvenç, H Vatansev, F Buğrul, F Gün, B Oran
Objective: Childhood obesity which is a predictor of adulthood obesity is associated with type 2 diabetes, metabolic syndrome, dyslipidemia, coronary artery diseases and subclinical inflammation. Growth differentiation factor-15, also known as macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the transforming growth factor- β super family and increases during inflammatory states. Adults with obesity have increased serum concentrations of MIC-1/GDF15. MIC-1/GDF15 is associated with cardio metabolic risk in adults...
October 17, 2016: Experimental and Clinical Endocrinology & Diabetes
Amit R Majithia, Ben Tsuda, Maura Agostini, Keerthana Gnanapradeepan, Robert Rice, Gina Peloso, Kashyap A Patel, Xiaolan Zhang, Marjoleine F Broekema, Nick Patterson, Marc Duby, Ted Sharpe, Eric Kalkhoven, Evan D Rosen, Inês Barroso, Sian Ellard, Sekar Kathiresan, Stephen O'Rahilly, Krishna Chatterjee, Jose C Florez, Tarjei Mikkelsen, David B Savage, David Altshuler
Clinical exome sequencing routinely identifies missense variants in disease-related genes, but functional characterization is rarely undertaken, leading to diagnostic uncertainty. For example, mutations in PPARG cause Mendelian lipodystrophy and increase risk of type 2 diabetes (T2D). Although approximately 1 in 500 people harbor missense variants in PPARG, most are of unknown consequence. To prospectively characterize PPARγ variants, we used highly parallel oligonucleotide synthesis to construct a library encoding all 9,595 possible single-amino acid substitutions...
October 17, 2016: Nature Genetics
Huei-Fen Jheng, Motohiko Hirotsuka, Tsuyoshi Goto, Masayuki Shibata, Yasuki Matsumura, Teruo Kawada
SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein- LFSMP-or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 weeks. Renal morphology and protein expression were evaluated by histochemical staining and western blots...
October 17, 2016: Molecular Nutrition & Food Research
Min Zhang, Zhongqi Zhou, Jinguang Wang, Shufa Li
Inflammatory pathways play an important role in impaired glucose metabolism and insulin production. Adipose tissue inflammation is characterized by infiltration and expansion of macrophages, leading to type 2 diabetes (T2D). Macrophage polarization contributes to various inflammatory responses and cytokine production profiles. MiR-130b is involved in regulating immune response and metabolism. However, the specific role in macrophage polarization and glucose metabolism of T2D has not been reported. In this study, C57BL/6 mice were fed a high-fat diet to induce T2D mice model...
October 13, 2016: Immunology Letters
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD(+)-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways...
October 15, 2016: Aging
Oleg Palygin, Daria V Ilatovskaya, Alexander Staruschenko
Protease-activated receptors (PARs) are a well-known family of transmembrane G-protein-coupled receptors (GPCRs). To date, four PARs have been identified and PAR1 and PAR2 are the most abundant receptors, which were shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligands that can be unmasked by serine protease cleavage. PARs are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular and inflammatory regulation of renal function in both normal and pathological conditions...
October 12, 2016: American Journal of Physiology. Renal Physiology
Tao Yan, Poornima Venkat, Michael Chopp, Alex Zacharek, Ruizhuo Ning, Cynthia Roberts, Yi Zhang, Mei Lu, Jieli Chen
BACKGROUND AND PURPOSE: Comorbidity of diabetes mellitus and stroke results in worse functional outcome, poor long-term recovery, and extensive vascular damage. We investigated the neurorestorative effects and mechanisms of stroke treatment with human bone marrow-derived mesenchymal stromal cells (hMSCs) in type 2 diabetes mellitus (T2DM) rats. METHODS: Adult male Wistar rats were induced with T2DM, subjected to 2 hours of middle cerebral artery occlusion (MCAo) and treated via tail-vein injection with (1) PBS (n=8) and (2) hMSCs (n=10; 5×10(6)) at 3 days after MCAo...
October 11, 2016: Stroke; a Journal of Cerebral Circulation
Fengming Liu, Rupam Sahoo, Xiaowen Ge, Lin Wu, Pamela Ghosh, Xuebin Qin, Jose A Halperin
AIMS: Clinical and experimental evidence supports a strong link between the complement system, complement regulatory proteins and the pathogenesis of diabetes vascular complications. We previously reported that the complement regulatory protein CD59 is inactivated by glycation in humans with diabetes. Our objective for this study is to assess experimentally how the deficiency of CD59 impacts the development of diabetic atherosclerosis in vivo. METHODS: We crossed mCD59 sufficient and deficient mice into the ApoE(-/-) background to generate mCd59ab(+/+)/ApoE(-/-) and mCd59ab(-/-)/ApoE(-/-) mice, and induced diabetes by multiple low dose injections of streptozotocin...
August 28, 2016: Journal of Diabetes and its Complications
Lingman Ma, Lifen Qian, Qidi Ying, Yan Zhang, Changlin Zhou, Guanzhong Wu
Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE(-/-) mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4...
October 7, 2016: Molecular and Cellular Endocrinology
Kai Sun, Jiyoung Park, Min Kim, Philipp E Scherer
Endotrophin is a cleavage product derived from the collagen VI(α3) chain. Collagen VI is expressed in a number of different tissues, but adipose tissue is a particularly prominent source for this extracellular matrix constituent. Mice lacking collagen VI are metabolically healthier due to reduced fibrosis in adipose tissue. Endotrophin seems to be one of the key players of collagen VI-mediated signalling effects, including its pro-fibrotic nature and chemoattractant properties for macrophages, while also playing an important role in cancer progression and the chemoresistance of tumour cells...
October 7, 2016: Diabetologia
Riki Toita, Takahito Kawano, Masaharu Murata, Jeong-Hun Kang
Obesity is associated with chronic inflammation and is known as a major risk factor for several diseases including chronic kidney disease, diabetes, and cardiovascular diseases. Macrophages play a critical role in the development of obesity-induced inflammation. Efficient delivery of therapeutic anti-inflammatory molecules, such as interleukin (IL)-10, to macrophages can dramatically improve therapeutic efficacy of obesity treatments. We used liposomes containing the 'eat-me' signal phosphatidylserine (PS) (PS-containing liposomes; PSL), which have macrophage targeting ability and anti-inflammatory functions, as a biomaterial carrier for the delivery of IL-10 to macrophages...
December 2016: Biomaterials
Javier A Carrero, Stephen T Ferris, Emil R Unanue
Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets...
October 3, 2016: Current Opinion in Immunology
Fang Yuan, Ryan Kolb, Gaurav Pandey, Wei Li, Lin Sun, Fuyou Liu, Fayyaz S Sutterwala, Yinghong Liu, Weizhou Zhang
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. The role of inflammation in DN has only recently been recognized. It has been shown that the NLRP3-inflammasome contributes to DN development by inducing interleukin (IL)-1β processing and secretion. In an effort to understand other IL-1β activating mechanism during DN development, we examined the role of the NLRC4-inflammasome in DN and found that NLRC4 is a parallel mechanism, in addition to the NLRP3-inflammasome, to induce pro-IL-1β processing and activation...
2016: PloS One
Blake J Cochran, Liming Hou, Anil Paul Chirackal Manavalan, Benjamin M Moore, Fatiha Tabet, Afroza Sultana, Luisa Cuesta Torres, Shudi Tang, Sudichhya Shrestha, Praween Senanayake, Mili Patel, William J Ryder, Andre Bongers, Marie Maraninchi, Valerie C Wasinger, Marit Westerterp, Alan R Tall, Philip J Barter, Kerry-Anne Rye
Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high glucose conditions and glucose disposal was shifted from skeletal muscle to adipose tissue...
October 4, 2016: Diabetes
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