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https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#1
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28434946/hyperglycemia-induced-renal-p2x7-receptor-activation-enhances-diabetes-related-injury
#2
Robert I Menzies, John W R Booth, John J Mullins, Matthew A Bailey, Frederick W K Tam, Jill T Norman, Robert J Unwin
Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1) has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R) are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40ml/min/1...
April 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28430795/igm-antibodies-to-oxidized-phosphatidylserine-as-protection-markers-in-cardiovascular-disease-among-60-year-olds
#3
Johan Frostegård, Jun Su, Sudhir Sing, Xiang Hua, Max Vikström, Karin Leander, Bruna Gigante, Ulf de Faire, Anna G Frostegård
OBJECTIVE: Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS: Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected...
2017: PloS One
https://www.readbyqxmd.com/read/28425844/the-role-of-glucose-6-phosphate-dehydrogenase-in-adipose-tissue-inflammation-in-obesity
#4
Yoon Jeong Park, Sung Sik Choe, Jee Hyung Sohn, Jae Bum Kim
Obesity is closely associated with metabolic diseases including type 2 diabetes. One hallmark characteristics of obesity is chronic inflammation that is coordinately controlled by complex signaling networks in adipose tissues. Compelling evidence indicates that reactive oxygen species (ROS) and its related signaling pathways play crucial roles in the progression of chronic inflammation in obesity. The pentose phosphate pathway (PPP) is an anabolic pathway that utilizes the glucoses to generate molecular building blocks and reducing equivalents in the form of NADPH...
February 8, 2017: Adipocyte
https://www.readbyqxmd.com/read/28421968/chronic-toxicology-studies-of-basal-insulin-peglispro-in-rats-and-dogs-a-novel-pegylated-insulin-lispro-analog-with-a-prolonged-duration-of-action
#5
Richard A Byrd, Jamie L Blackbourne, Mary Pat Knadler, Albert E Schultze, John L Vahle
Basal insulin peglispro (BIL) consists of insulin lispro with a 20-kDa polyethylene glycol (PEG) moiety covalently attached to lysine B28. Because chronic parenteral administration of PEGylated proteins to animals has sometimes resulted in PEG vacuolation of tissue macrophages, renal tubular cells, and choroid plexus ependymal cells, we investigated whether chronic subcutaneous (sc) injection of BIL in rats (52 weeks) and dogs (39 weeks) was associated with systemic toxicities or other changes, including vacuolation of tissue macrophages, renal tubular cells, and ependymal cells...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28420816/coronary-atherosclerotic-plaque-characteristics-and-cardiovascular-risk-factors%C3%A3-insights-from-an-optical-coherence-tomography-study
#6
Roberta De Rosa, Mariuca Vasa-Nicotera, David M Leistner, Sophia M Reis, Claudia E Thome, Jes-Niels Boeckel, Stephan Fichtlscherer, Andreas M Zeiher
BACKGROUND: The association between cardiovascular risk factors (CVRF) and the risk of coronary events is widely acknowledged. Whether individual risk factors may be associated with distinct plaque characteristics is currently unclear. We investigated the relationship between CVRF and coronary plaque burden and phenotype.Methods and Results:We assessed coronary atherosclerotic plaque characteristics by optical coherence tomography in 67 patients with stable coronary artery disease undergoing coronary angiography...
April 14, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28420094/nonalcoholic-fatty-liver-disease-and-insulin-resistance-new-insights-and-potential-new-treatments
#7
REVIEW
Hironori Kitade, Guanliang Chen, Yinhua Ni, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28419534/endocrine-imbalance-associated-with-proteome-changes-in-diabetes
#8
Amr A Sayed, Ahmed M Alhawary, Aboalela Farag, Dina R Johar, Larry H Bernstein
The dynamics of cellular metabolism involves rapid interactions between proteins and nucleotides, proteins and proteins, proteins and mRNA, the action of miRNA, and signaling. These also involve the interactions with respect to the sulfur bond, oxygen radicals that initiate a change in conformation and a chain of events. We review a development in molecular medicine that is a very promising work in progress. We also review the current and future research methods involving mitochondria. Long-term effects of diabetes include glycation of proteins, e...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28416579/inflammatory-stimuli-induce-acyl-coa-thioesterase-7-and-remodeling-of-phospholipids-containing-unsaturated-long-%C3%A2-c20-acyl-chains-in-macrophages
#9
Valerie Z Wall, Shelley Barnhart, Farah Kramer, Jenny E Kanter, Anuradha Vivekanandan-Giri, Subramaniam Pennathur, Chiara Bolego, Jessica M Ellis, Miguel A Gijón, Michael J Wolfgang, Karin E Bornfeldt
Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl-CoAs to free fatty acids. ACOT7 is induced by lipopolysaccharide (LPS), thus we investigated downstream effects of LPS-induced induction of ACOT7 and its role in inflammatory settings in myeloid cells. Enzymatic thioesterase activity assays in wildtype and ACOT7-deficient macrophage lysates indicated that endogenous ACOT7 contributes a significant fraction of total acyl-CoA thioesterase activity towards C20:4-CoA, C20:5-CoA and C22:6-CoA, but contributes little activity towards shorter acyl-CoA species...
April 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28414075/vitamin-b2-deficiency-enhances-the-pro-inflammatory-activity-of-adipocyte-consequences-for-insulin-resistance-and-metabolic-syndrome-development
#10
Agnieszka Irena Mazur-Bialy, Ewa Pocheć
AIMS: Adipose tissue is an endocrine organ important for regulation of such physiological processes as energy metabolism or lipids homeostasis. In an obesity state, it participates in the induction of chronic systemic inflammation accompanied by pro-inflammatory cytokines and fatty acid elevation. For this reasons, adipose tissue is involved in, e.g., insulin resistance, type 2 diabetes or hyperlipidemia development. In our previous study, we have shown that riboflavin deficiency induces a pathological pro-inflammatory response of macrophages, the main component of adipose tissue...
April 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28410399/altered-glucose-metabolism-and-hypoxic-response-in-alloxan-induced-diabetic-atherosclerosis-in-rabbits
#11
Yunosuke Matsuura, Atsushi Yamashita, Yan Zhao, Takashi Iwakiri, Kazuaki Yamasaki, Chihiro Sugita, Chihiro Koshimoto, Kazuo Kitamura, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
Diabetes mellitus accelerates atherosclerosis that causes most cardiovascular events. Several metabolic pathways are considered to contribute to the development of atherosclerosis, but comprehensive metabolic alterations to atherosclerotic arterial cells remain unknown. The present study investigated metabolic changes and their relationship to vascular histopathological changes in the atherosclerotic arteries of rabbits with alloxan-induced diabetes. Diabetic atherosclerosis was induced in rabbit ilio-femoral arteries by injecting alloxan (100 mg/kg), injuring the arteries using a balloon, and feeding with a 0...
2017: PloS One
https://www.readbyqxmd.com/read/28408925/combination-therapy-with-a-sodium-glucose-cotransporter-2-inhibitor-and-a-dipeptidyl-peptidase-4-inhibitor-additively-suppresses-macrophage-foam-cell-formation-and-atherosclerosis-in-diabetic-mice
#12
Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, Tsutomu Hirano
Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe(-/-) ) mice...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28408068/quercus-infectoria-inhibits-set7-nf-%C3%AE%C2%BAb-inflammatory-pathway-in-macrophages-exposed-to-a-diabetic-environment
#13
Julalak Chokpaisarn, Norifumi Urao, Supayang P Voravuthikunchai, Timothy J Koh
Chronic inflammation plays a key role in the pathogenesis of myriad complications associated with diabetes and thus anti-inflammatory therapies may ameliorate these complications. Quercus infectoria (Qi) extract has been shown to downregulate inflammatory processes; however, the molecular mechanisms of this anti-inflammatory activity remain unclear. The hypothesis of our study was that Qi extract exerts its anti-inflammatory effect by downregulating the Set7/NF-κB pathway. Bone marrow-derived macrophages (BMM) were treated with high glucose plus palmitate medium (HG/Pa) to simulate the diabetic environment...
April 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28406702/an-alternatively-activated-macrophage-marker-cd163-in-severely-obese-patients-the-influence-of-very-low-calorie-diet-and-bariatric-surgery
#14
A Cinkajzlová, Z Lacinová, J Kloučková, P Kaválková, P Trachta, M Kosák, J Krátký, M Kasalický, K DoleŽalová, M Mráz, M Haluzík
CD163 is a marker of macrophages with anti-inflammatory properties and its soluble form (sCD163) is considered a prognostic predictor of several diseases including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We also assessed the changes of CD163 positive cells of monocyte-macrophage lineage in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28399645/prohibitin-at-the-crossroads-of-obesity-linked-diabetes-and-cancer
#15
Suresh Mishra, Bl Grégoire Nyomba
The promoter of a gene that is selectively expressed in just a few cell types provides unique opportunities to study: (1) the pleiotropic function of a protein in two different cell types including the cell compartment specific function, and (2) the crosstalk between two cell/tissue types at the systemic level. This is not possible with a ubiquitous or a highly specific gene promoter. The adipocyte protein-2 ( aP2) is one such gene. It is primarily expressed in adipocytes, but also selectively in monocytic macrophages and dendritic cells, among various immune cell types...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28398495/a-histological-study-of-fulminant-type-1-diabetes-mellitus-related-to-human-cytomegalovirus-reactivation
#16
Sho Yoneda, Akihisa Imagawa, Kenji Fukui, Sae Uno, Junji Kozawa, Makoto Sakai, Toshiki Yumioka, Hiromi Iwahashi, Iichiro Shimomura
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: We determined the localization of viruses of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells by immunohistochemistry of pancreas from an autopsy fulminant T1DM patient with DIHS or seven subjects with normal glucose tolerance who underwent pancreatectomy...
April 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28396116/beta-2-adrenergic-receptor-agonists-are-novel-regulators-of-macrophage-activation-in-diabetic-renal-and-cardiovascular-complications
#17
Hyunjin Noh, Mi Ra Yu, Hyun Joo Kim, Ji Hye Lee, Byoung-Won Park, I-Hsien Wu, Motonobu Matsumoto, George L King
Macrophage activation is increased in diabetes and correlated with the onset and progression of vascular complications. To identify drugs that could inhibit macrophage activation, we developed a cell-based assay and screened a 1,040 compound library for anti-inflammatory effects. Beta2-adrenergic receptor (β2AR) agonists were identified as the most potent inhibitors of phorbol myristate acetate-induced tumor necrosis factor-α production in rat bone marrow macrophages. In peripheral blood mononuclear cells isolated from streptozotocin-induced diabetic rats, β2AR agonists inhibited diabetes-induced tumor necrosis factor-α production, which was prevented by co-treatment with a selective β2AR blocker...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28395010/inflammation-and-metabolic-cardiomyopathy
#18
Kazuhiko Nishida, Kinya Otsu
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status...
March 15, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28394269/ginkgolide-a-ameliorates-lps-induced-inflammatory-responses-in-vitro-and-in-vivo
#19
Yan Li, Yannan Wu, Xinlei Yao, Fang Hao, Chunlei Yu, Yongli Bao, Yin Wu, Zhenbo Song, Ying Sun, Lihua Zheng, Guannan Wang, Yanxin Huang, Luguo Sun, Yuxin Li
Ginkgolide A (GA) is a natural compound isolated from Ginkgo biloba and has been used to treat cardiovascular diseases and diabetic vascular complications. However, only a few studies have been conducted on the anti-inflammatory effects of GA. In particular, no related reports have been published in a common inflammation model of lipopolysaccharide (LPS)-stimulated macrophages, and the anti-inflammatory mechanisms of GA have not been fully elucidated. In the present study, we extensively investigated the anti-inflammatory potential of GA in vitro and in vivo...
April 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28392574/m2-specific-reduction-of-cd1d-switches-nkt-cell-mediated-immune-responses-and-triggers-metaflammation-in-adipose-tissue
#20
Huimin Zhang, Rufeng Xue, Shasha Zhu, Sicheng Fu, Zuolong Chen, Rongbin Zhou, Zhigang Tian, Li Bai
Metaflammation is responsible for several metabolic syndromes, such as type 2 diabetes. However, the mechanisms by which metabolic disorders trigger metaflammation remain unclear. We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues. A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages...
April 10, 2017: Cellular & Molecular Immunology
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