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Insulin and atherosclerosis

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https://www.readbyqxmd.com/read/27920123/selective-enhancement-of-insulin-sensitivity-in-the-endothelium-in-vivo-reveals-a-novel-proatherosclerotic-signalling-loop
#1
Hema Viswambharan, Nadira Y Yuldasheva, Anshuman Sengupta, Helen Imrie, Matthew C Gage, Natalie J Haywood, Andrew M Walker, Anna Skromna, Natalia Makova, Stacey L Galloway, Pooja Shah, Piruthivi Sukumar, Karen E Porter, Peter J Grant, Ajay M Shah, Celio X Santos, Jing Li, David J Beech, Stephen Wheatcroft, Richard M Cubbon, Mark T Kearney
RATIONALE: In the endothelium, insulin stimulates endothelial nitric oxide synthase (eNOS) to generate the anti-atherosclerotic signalling radical NO. Insulin resistant type 2 diabetes is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear. OBJECTIVE: To answer this question we generated a mouse with endothelial cell (EC)-specific over-expression of the human insulin receptor (hIRECO) using the Tie2 promoter-enhancer...
December 5, 2016: Circulation Research
https://www.readbyqxmd.com/read/27919218/a-glycemic-threshold-of-90-mg-dl-promotes-early-signs-of-atherosclerosis-in-apparetly-healthy-overweight-obese-subjects
#2
Marco Matteo Ciccone, Francesca Cortese, Michele Gesualdo, Ilaria Donvito, Santa Carbonara, Giovanni De Pergola
BACKGROUND: Alterations of glucose metabolism represent well known risk factors for the atherosclerotic process and then for cardiovascular disease. OBJECTIVE: to investigate the association between fasting glucose and early signs of atherosclerosis, by means of carotid intima-media thickness (c-IMT) in a population of apparently healthy overweight/obese subjects. In addition, we evaluated the possible existence of a glycemic threshold above which the risk of atherosclerosis significantly increases...
December 5, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/27908890/pathology-of-human-coronary-and-carotid-artery-atherosclerosis-and-vascular-calcification-in-diabetes-mellitus
#3
Kazuyuki Yahagi, Frank D Kolodgie, Christoph Lutter, Hiroyoshi Mori, Maria E Romero, Aloke V Finn, Renu Virmani
The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27906549/anti-inflammatory-and-ros-suppressive-effects-of-the-addition-of-fiber-to-a-high-fat-high-calorie-meal
#4
Husam Ghanim, Manav Batra, Sanaa Abuaysheh, Kelly Green, Antoine Makdissi, Nitesh Kuhadiya, Ajay Chaudhuri, Paresh Dandona
BACKGROUND: Fiber intake is associated with a reduction in the occurrence of cardiovascular events and diabetes. OBJECTIVE: To investigate whether the addition of fiber to a high fat-high Calorie (HFHC) meal prevents pro-inflammatory changes induced by HFHC meal. DESIGN: Ten fasting normal subjects consumed HFHC meal with or without an additional 30g of insoluble dietary fiber on 2 separate visits. Blood samples were collected over 5hr and mononuclear cells (MNC) isolated...
December 1, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27905925/expression-of-insulin-receptor-ir-a-and-b-isoforms-igf-ir-and-ir-igf-ir-hybrid-receptors-in-vascular-smooth-muscle-cells-and-their-role-in-cell-migration-in-atherosclerosis
#5
N Beneit, C E Fernández-García, J L Martín-Ventura, L Perdomo, Ó Escribano, J B Michel, G García-Gómez, S Fernández, S Díaz-Castroverde, J Egido, A Gómez-Hernández, M Benito
BACKGROUND: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic process. In a previous work, we demonstrated that the insulin receptor isoform A (IRA) and its association with the insulin-like growth factor-I receptor (IGF-IR) confer a proliferative advantage to VSMCs. However, the role of IR and IGF-IR in VSMC migration remains poorly understood. METHODS: Wound healing assays were performed in VSMCs bearing IR (IRLoxP(+/+) VSMCs), or not (IR(-/-) VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs)...
December 1, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27905124/assessment-of-early-atherosclerosis-and-left-ventricular-dysfunction-in-children-with-21-hydroxylase-deficiency
#6
Rahmi Özdemir, Hüseyin Anil Korkmaz, Mehmet Küçük, Cem Karadeniz, Timur Meşe, Behzat Özkan
AIM: We analysed 25 children with 21-hydroxylase deficiency who received glucocorticoid and/or mineralocorticoid treatment for at least 12 months to determine the effects of the disease and its treatment on vascular structures and ventricular function. METHODS: Twenty-five patients with 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) and 25 control subjects were enrolled into this observational, cross-sectional study. The patients were investigated in terms of fasting blood glucose and insulin; fasting serum lipid profile; serum 17-hydroxyprogesterone; dehydroepiandrosterone sulphate; androstenedione; and adrenocorticotropic hormone...
November 7, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/27904611/selective-serotonin-reuptake-inhibitors-and-cardiovascular-events-a-systematic-review
#7
REVIEW
Mohammad Hassan Nezafati, Ali Eshraghi, Mohammad Vojdanparast, Saeed Abtahi, Pouya Nezafati
BACKGROUND: Given the importance of the role of depression in predicting the outcome of cardiovascular disorders, current medications for treating depression, particularly selective serotonin reuptake inhibitors (SSRIs), are taken into consideration. This study aimed to systematically review the published findings in the use of SSRIs and the risk for cardiac events. MATERIALS AND METHODS: An independent review of the Web of Science, PubMed, Scopus, Cochrane, CINAHL, index Copernicus, and Google Scholar, up to 2014, was performed...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27899247/association-of-plasma-fetuin-a-levels-with-peripheral-arterial-disease-and-lower-extremity-arterial-calcification-in-subjects-with-type-2-diabetes-mellitus
#8
Ioanna Eleftheriadou, Pinelopi Grigoropoulou, Alexander Kokkinos, Iordanis Mourouzis, Despoina Perrea, Nicholas Katsilambros, Petros P Sfikakis, Nikolaos Tentolouris
AIMS: Fetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle-brachial index (ABI) was calculated...
November 12, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27898058/ccl5-rantes-contributes-to-hypothalamic-insulin-signaling-for-systemic-insulin-responsiveness-through-ccr5
#9
Szu-Yi Chou, Reni Ajoy, Chun Austin Changou, Ya-Ting Hsieh, Yang-Kao Wang, Barry Hoffer
Many neurodegenerative diseases are accompanied by metabolic disorders. CCL5/RANTES, and its receptor CCR5 are known to contribute to neuronal function as well as to metabolic disorders such as type 2 diabetes mellitus, obesity, atherosclerosis and metabolic changes after HIV infection. Herein, we found that the lack of CCR5 or CCL5 in mice impaired regulation of energy metabolism in hypothalamus. Immunostaining and co-immunoprecipitation revealed the specific expression of CCR5, associated with insulin receptors, in the hypothalamic arcuate nucleus (ARC)...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#10
Jacob M Keaton, Jacklyn N Hellwege, Maggie C Y Ng, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-DER I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Donald W Bowden
Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492 subjects)...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27894808/protective-effect-of-betulinic-acid-on-early-atherosclerosis-in-diabetic-apolipoprotein-e-gene-knockout-mice
#11
Jung Joo Yoon, Yun Jung Lee, Byung Hyuk Han, Eun Sik Choi, Min Chul Kho, Ji Hun Park, You Mee Ahn, Hye Yoom Kim, Dae Gill Kang, Ho Sub Lee
Atherosclerosis, a chronic and progressive disease, is a leading cause of endothelial dysfunction, diabetes mellitus, hypertension, and hypercholesterolemia. Betulinic acid (BA), a pentacyclic triterpene, has been reported to have a variety of biological effects, including anti-inflammatory and immunomodulatory properties. This study was designed to determine whether BA could prevent atherosclerosis in diabetic apolipoprotein-E gene knockout (ApoE KO) mice. The mice were treated with BA for 12 weeks to examine its beneficial effects on atherosclerosis in ApoE KO mice...
November 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27889764/high-uric-acid-activates-the-ros-ampk-pathway-impairs-cd68-expression-and-inhibits-oxldl-induced-foam-cell-formation-in-a-human-monocytic-cell-line-thp-1
#12
Chaohuan Luo, Xueke Lian, Liangli Hong, Jingfang Zou, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Yaqiu Hu, Huier Yuan, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Ichiro Hisatome, Tetsuya Yamamoto, Jiexiong Huang, Jidong Cheng
BACKGROUND/AIMS: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA) exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL)-induced foam-cell formation in a human monocytic cell line, THP-1...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27881128/effect-of-intensive-insulin-treatment-on-plasma-levels-of-lipoprotein-associated-phospholipase-a2-and-secretory-phospholipase-a2-in-patients-with-newly-diagnosed-type-2-diabetes
#13
Xiu-Hong Lin, Ming-Tong Xu, Jv-Ying Tang, Li-Fang Mai, Xiao-Yi Wang, Meng Ren, Li Yan
BACKGROUND: China has the highest absolute disease burden of diabetes worldwide. For diabetic patients, diabetes-related vascular complications are major causes of morbidity and mortality. The roles of lipoprotein-associated phospholipase A2 (Lp-PLA2) and secretory phospholipase A2 (sPLA2) as inflammatory markers have been recently evaluated in the pathogenesis of both diabetes and atherosclerosis. We aimed to determine the mechanism through which patients with newly diagnosed type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by evaluating the change in Lp-PLA2 and sPLA2 levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic β-cell function...
November 23, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27872172/urea-a-true-uremic-toxin-the-empire-strikes-back
#14
REVIEW
Wei Ling Lau, Nosratola D Vaziri
Blood levels of urea rise with progressive decline in kidney function. Older studies examining acute urea infusion suggested that urea was well-tolerated at levels 8-10× above normal values. More recent in vitro and in vivo work argue the opposite and demonstrate both direct and indirect toxicities of urea, which probably promote the premature aging phenotype that is pervasive in chronic kidney disease (CKD). Elevated urea at concentrations typically encountered in uremic patients induces disintegration of the gut epithelial barrier, leading to translocation of bacterial toxins into the bloodstream and systemic inflammation...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27866224/the-beneficial-effects-of-empagliflozin-an-sglt2-inhibitor-on-atherosclerosis-in-apoe-mice-fed-a-western-diet
#15
Ji Hye Han, Tae Jung Oh, Ghayoung Lee, Hyo Jin Maeng, Dong Hwa Lee, Kyoung Min Kim, Sung Hee Choi, Hak Chul Jang, Hye Seung Lee, Kyong Soo Park, Young-Bum Kim, Soo Lim
AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE (-/-) mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0...
November 19, 2016: Diabetologia
https://www.readbyqxmd.com/read/27862873/the-sustained-influence-of-metformin-therapy-on-circulating-glp-1-levels-in-individuals-with-and-without-type-2-diabetes
#16
David Preiss, Adem Dawed, Paul Welsh, Alison Heggie, Angus G Jones, Jacqueline Dekker, Robert Koivula, Tue H Hansen, Ms Caitlin Stewart, Rury R Holman, Paul W Franks, Mark Walker, Ewan R Pearson, Naveed Sattar
AIMS: Small, short studies suggest metformin influences the glucagon-like peptide (GLP)-1 axis in individuals with and without type 2 diabetes (T2DM). In the Carotid Atherosclerosis: Metformin for insulin ResistAnce (CAMERA) trial (NCT00723307) we investigated whether this effect is sustained and related to changes in glycaemia or weight. In the cross-sectional DIabetes REsearCh on patient straTification (DIRECT) study, we investigated basal and post-meal GLP-1 levels in diabetic patients...
November 13, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27860077/critical-in-vivo-roles-of-histamine-and-histamine-receptor-signaling-in-animal-models-of-metabolic-syndrome
#17
REVIEW
Sohsuke Yamada, Akihide Tanimoto, Yasuyuki Sasaguri
Histamine, a classic low-molecular-weight amine, is synthesized from L-histidine by histidine decarboxylase (HDC), and histamine-specific receptors (HRs) are essential for its actions. Our serial in vivo studies have uniquely reported that expression of histamine/HRs is variably identified in atherosclerotic lesions, and that HDC-gene knockout mice without histamine/HRs signaling show a marked reduction of atherosclerotic progression. These data have convinced us that histamine plays a pivotal role in the pathogenesis of atherosclerosis...
December 2016: Pathology International
https://www.readbyqxmd.com/read/27858577/long-term-endurance-training-increases-serum-cathepsin-s-and-decreases-il-6-and-hscrp-levels
#18
Michael Sponder, Ioana-Alexandra Campean, Michael Emich, Monika Fritzer-Szekeres, Brigitte Litschauer, Jutta Bergler-Klein, Senta Graf, Jeanette Strametz-Juranek
Cathepsin S (CS) was shown to play a key role in cancer progression, atherosclerosis, heart valve disease, insulin resistance and diabetes mellitus. The present prospective study aimed to investigate the influence of sports on CS, interleukin-6 (Il-6) and high-sensitivity C-reactive protein (hsCRP) levels. Ninety-eight of 109 participants completed the study. Ergometries were performed at baseline and after 8 months to evaluate/quantify the performance gain. Blood samples were taken at baseline and every 2 months...
November 18, 2016: Journal of Sports Sciences
https://www.readbyqxmd.com/read/27856635/micrornaa-155-deficiency-leads-to-decreased-atherosclerosis-increased-white-adipose-tissue-obesity-and-nonalcoholic-fatty-liver-disease-a-novel-mouse-model-of-obesity-paradox
#19
Anthony Virtue, Candice Johnson, Jahaira Lopez-Pastraña, Ying Shao, Hangfei Fu, Xinyuan Li, Ya-Feng Li, Ying Yin, Jietang Mai, Victor Rizzo, Michael Tordoff, Zsolt Bagi, Huimin Shan, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Obesity paradox (OP) describes a widely observed clinical finding of improved cardiovascular fitness and survival in some overweight or obese patients. The molecular mechanisms underlying OP remain enigmatic partly due to a lack of animal models mirroring OP in patients. Using apolipoprotein E knockout (ApoE-/-) mice on high-fat (HF) diet as an atherosclerotic obesity model, we demonstrated: 1) microRNA-155 (miRNA-155, miR-155) is significantly upregulated in aortas of ApoE-/- mice; and miR-155 deficiency in ApoE-/- mice inhibits atherosclerosis; 2) ApoE-/-/miR-155-/- (DKO) mice show HF diet-induced obesity, adipocyte hypertrophy and present with nonalcoholic fatty liver disease (NAFLD); 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin, increased expression of adipogenic transcription factors, but lack glucose intolerance and insulin resistance...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27856349/reparative-effects-of-interleukin-1-receptor-antagonist-in-young-and-aged-co-morbid-rodents-after-cerebral-ischemia
#20
Jesus M Pradillo, Katie N Murray, Graham A Coutts, Ana Moraga, Fernando Oroz-Gonjar, Herve Boutin, Maria A Moro, Ignacio Lizasoain, Nancy J Rothwell, Stuart M Allan
Neuroprotective strategies for ischemic stroke have failed to translate from bench to bedside, possibly due to the lack of consideration of key clinical co-morbidities. Stroke and co-morbidities are associated with raised levels of the pro-inflammatory cytokine interleukin-1 (IL-1). Inhibition of IL-1 by the administration of interleukin-1 receptor antagonist (IL-1Ra) has shown to be neuroprotective after experimental cerebral ischemia. Stroke can also trigger a robust neuroreparative response following injury, yet many of these new born neurons fail to survive or integrate into pre-existing circuits...
November 14, 2016: Brain, Behavior, and Immunity
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