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https://www.readbyqxmd.com/read/27919931/low-mt-co1-in-monocytes-and-microvesicles-is-associated-with-outcome-in-patients-with-coronary-artery-disease
#1
Paul Holvoet, Maarten Vanhaverbeke, Katarzyna Bloch, Pieter Baatsen, Peter Sinnaeve, Stefan Janssens
BACKGROUND: Cytochrome oxidase (COX) IV complex regulates energy production in mitochondria. Impaired COX gene expression is related to obesity and type 2 diabetes mellitus, but whether it is directly related to the incidence of cardiovascular events is unknown. We investigated whether COX gene expression in monocytes is predictive for cardiovascular events in coronary artery disease patients. To avoid monocyte isolation from fresh blood, we then aimed to validate our findings in monocyte-derived microvesicles isolated from plasma...
December 5, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27914922/negative-regulation-of-hepatic-fat-mass-and-obesity-associated-fto-gene-expression-by-insulin
#2
Tooru M Mizuno, Pei San Lew, Yanming Luo, Arnold Leckstrom
AIMS: To investigate the role of glucose and insulin in the regulation of hepatic fat mass and obesity associated (Fto) gene expression and the role of hepatic Fto in the regulation of gluconeogenic gene expression. MAIN METHODS: To determine the effect of hyperglycemia on hepatic Fto expression, levels of Fto mRNA in liver were compared between normoglycemic/normoinsulinemic, hypereglycemic/hyperinsulinemic, and hyperglycemic/hypoinsulinemic mice. To determine the direct effect of insulin on Fto expression, levels of Fto, glucose-6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (Pepck) mRNA levels were compared between control and insulin-treated mouse liver tissues cultured ex vivo and immortalized mouse hepatocytes AML12...
November 30, 2016: Life Sciences
https://www.readbyqxmd.com/read/27914538/adaptive-response-of-rat-pancreatic-%C3%AE-cells-to-insulin-resistance-induced-by-monocrotophos-biochemical-evidence
#3
Raju Nagaraju, Padmanabhan Sharda Rajini
Our previous findings clearly suggested the role of duration of exposure to monocrotophos (MCP) in the development of insulin resistance. Rats exposed chronically to MCP developed insulin resistance with hyperinsulinemia without overt diabetes. In continuation of this vital observation, we sought to delineate the biochemical mechanisms that mediate heightened pancreatic β-cell response in the wake of MCP-induced insulin resistance in rats. Adult rats were orally administered (0.9 and 1.8mg/kgb.w/d) MCP for 180days...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27909574/characterization-of-5-2-18-f-fluoroethoxy-l-tryptophan-for-pet-imaging-of-the-pancreas
#4
Ahmed Abbas, Christine Beamish, Rebecca McGirr, John Demarco, Neil Cockburn, Dawid Krokowski, Ting-Yim Lee, Michael Kovacs, Maria Hatzoglou, Savita Dhanvantari
Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- (18)F-fluoroethoxy)-L-tryptophan ( (18)F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of (18)F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution...
2016: F1000Research
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#5
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903643/effects-of-antihypertensive-agents-on-intestinal-contractility-in-the-spontaneously-hypertensive-rat-angiotensin-receptor-system-down-regulation-by-losartan
#6
Glen S Patten, Mahinda Y Abeywardena
Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus and recently to dysfunction of the gut. The aim of this study was to determine what effect anti-hypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment SHR were treated with enalapril or hydralazine. In the second experiment SHR were treated with losartan with no-treatment as control for both experiments...
November 30, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27898284/increased-vldl-tg-fatty-acid-storage-in-skeletal-muscle-in-men-with-type-2-diabetes
#7
Iben R Andersen, Esben Søndergaard, Lars P Sørensen, Birgitte Nellemann, Lars C Gormsen, Michael D Jensen, Søren Nielsen
CONTEXT: Lipoprotein lipase (LPL) activity is considered the rate-limiting step of very-low-density-lipoprotein triglycerides (VLDL-TG) tissue storage, and has been suggested to relate to the development of obesity as well as insulin resistance and type 2 diabetes. OBJECTIVE: The objective of the study was to assess the relationship between the quantitative storage of VLDL-TG fatty acids and LPL activity and other storage factors in muscle and adipose tissue. In addition, we examine whether such relations were influenced by type 2 diabetes...
November 29, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27898058/ccl5-rantes-contributes-to-hypothalamic-insulin-signaling-for-systemic-insulin-responsiveness-through-ccr5
#8
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/27895989/diet-induced-obesity-skin-changes-monitored-by-in-vivo-shg-and-ex-vivo-cars-microscopy
#9
Dóra Haluszka, Kende Lőrincz, Norbert Kiss, Róbert Szipőcs, Enikő Kuroli, Nóra Gyöngyösi, Norbert M Wikonkál
Obesity related metabolic syndrome and type 2 diabetes have severe consequences on our skin. Latest developments in nonlinear microscopy allow the use of noninvasive, label free imaging methods, such as second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS), for early diagnosis of metabolic syndrome-related skin complications by 3D imaging of the skin and the connective tissue. Our aim was to study effects of various types of diet-induced obesity in mice using these methods. We examined mice on different diets for 32 weeks...
November 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27882442/the-effects-of-zofenopril-on-cardiac-function-and-pro-oxidative-parameters-in-the-streptozotocin-induced-diabetic-rat-heart
#10
Petar Ristic, Ivan Srejovic, Tamara Nikolic, Isidora Stojic, Dragana Ristic, Vladimir Zivkovic, Vladimir Lj Jakovljevic
Diabetes mellitus is a chronic condition that continues to increase in both incidence and prevalence. Renin-Angiotensin-Aldosterone System is one of the main modulators of chronic hyperglycaemia and, thus, its influence on tissues. Hyperglycaemia-induced oxidative stress is an important factor in diabetic cardiomyopathy. The present study was carried out on 24 adult male Wistar albino rats (8-week-old and with body masses of 190 ± 10 g). We evaluated the influence of acute administration of zofenopril on ex vivo myocardial function from rats with streptozotocin-induced diabetes mellitus, with a special emphasis on cardiodynamic and oxidative stress parameters in diabetic rat hearts...
November 24, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27881707/a-cd80-biased-ctla4-ig-fusion-protein-with-superior-in-vivo-efficacy-by-simultaneous-engineering-of-affinity-selectivity-stability-and-fcrn-binding
#11
Julie Douthwaite, Jacques Moisan, Cyril Privezentzev, Blagoje Soskic, Shereen Sabbah, Suzanne Cohen, Andie Collinson, Elizabeth England, Catherine Huntington, Ben Kemp, Li Zhuang, Suzanne Hudak, D Gareth Rees, Debbie Goldberg, Chris Barton, Linda Chang, Inna Vainshtein, Meina Liang, Laurie Iciek, Philip Ambery, Mark Peakman, Tristan J Vaughan, Tim I M Tree, David M Sansom, Michael A Bowen, Ralph R Minter, Lutz Jermutus
Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies with the potential of higher efficacy and greater convenience to patients. In this study, to our knowledge, we have, for the first time, used in vitro evolution to simultaneously optimize CTLA4 affinity and stability. We selected for improved binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions directly in functional assays to identify variants with stronger suppression of in vitro T cell activation...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27872157/exendin-4-increases-oxygen-consumption-and-thermogenic-gene-expression-in-muscle-cells
#12
Jin-Seung Choung, Young-Sun Lee, Hee-Sook Jun
Glucagon-like peptide-1 (GLP1) has many anti-diabetic actions and also increases energy expenditure in vivo. Since skeletal muscle is a major organ controlling energy metabolism, we investigated whether GLP1 can affect energy metabolism in muscle. We found that treatment of differentiated C2C12 cells with Exendin-4 (Ex-4), a GLP1 receptor agonist, reduced oleate:palmitate-induced lipid accumulation and triglyceride content compared with cells without Ex-4 treatment. When we examined the oxygen consumption rate (OCR), not only the basal OCR but also the OCR induced by oleate:palmitate addition was significantly increased in Ex-4-treated differentiated C2C12 cells, and this was inhibited by Exendin-9, a GLP1 receptor antagonist...
November 21, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27865831/rutin-suppresses-human-amylin-hiapp-misfolding-and-oligomer-formation-in-vitro-and-ameliorates-diabetes-and-its-impacts-in-human-amylin-hiapp-transgenic-mice
#13
Jacqueline F Aitken, Kerry M Loomes, Isabel Riba-Garcia, Richard D Unwin, Gordana Prijic, Ashley S Phillips, Anthony R J Phillips, Donghai Wu, Sally D Poppitt, Ke Ding, Perdita E Barran, Andrew W Dowsey, Garth J S Cooper
Pancreatic islet β-cells secrete the hormones insulin and amylin, and defective β-cell function plays a central role in the pathogenesis of type-2 diabetes (T2D). Human amylin (hA, also termed hIAPP) misfolds and forms amyloid aggregates whereas orthologous mouse amylin does neither. Furthermore, hA elicits apoptosis in cultured β-cells and β-cell death in ex-vivo islets. In addition, hA-transgenic mice that selectively express hA in their β-cells, manifest β-cell apoptosis and progressive islet damage that leads to diabetes closely resembling that in patients with T2D...
November 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27854328/parenchymal-and-stromal-cells-contribute-to-pro-inflammatory-myocardial-environment-at-early-stages-of-diabetes-protective-role-of-resveratrol
#14
Monia Savi, Leonardo Bocchi, Roberto Sala, Caterina Frati, Costanza Lagrasta, Denise Madeddu, Angela Falco, Serena Pollino, Letizia Bresciani, Michele Miragoli, Massimiliano Zaniboni, Federico Quaini, Daniele Del Rio, Donatella Stilli
Background: Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. Methods: In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues...
November 16, 2016: Nutrients
https://www.readbyqxmd.com/read/27852684/resveratrol-as-add-on-therapy-in-subjects-with-well-controlled-type-2-diabetes-a-randomized-controlled-trial
#15
Silvie Timmers, Marlies de Ligt, Esther Phielix, Tineke van de Weijer, Jan Hansen, Esther Moonen-Kornips, Gert Schaart, Iris Kunz, Matthijs K C Hesselink, Vera B Schrauwen-Hinderling, Patrick Schrauwen
OBJECTIVE: To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of standard diabetes care. RESEARCH DESIGN AND METHODS: Seventeen subjects with well-controlled type 2 diabetes (T2D) were treated with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique...
December 2016: Diabetes Care
https://www.readbyqxmd.com/read/27836811/sirt1-ampk-crosstalk-is-involved-in-high-glucose-dependent-impairment-of-insulin-responsiveness-in-primary-rat-podocytes
#16
Dorota Rogacka, Agnieszka Piwkowska, Irena Audzeyenka, Stefan Angielski, Maciej Jankowski
Growing evidence indicates that in diabetes, high glucose concentrations affect podocyte metabolism and function. The crucial pathological feature of type 2 diabetes mellitus and metabolic syndrome is insulin resistance, often developed as a result of dysregulation of nutrient-responsible systems and disturbance of cellular homeostasis under diabetic conditions. Here, we report the involvement of the reciprocal interplay between deacetylase SIRT1 and protein kinase AMPK in podocyte high glucose-induced abolition of insulin-dependent glucose uptake, manifesting insulin resistance...
November 9, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27832861/perilipin-1-binds-to-aquaporin-7-in-human-adipocytes-and-controls-its-mobility-via-protein-kinase-a-mediated-phosphorylation
#17
Jesper S Hansen, Christian Krintel, Malin Hernebring, Tatu J K Haataja, Sofia de Marè, Sebastian Wasserstrom, Urszula Kosinska-Eriksson, Madelene Palmgren, Cecilia Holm, Karin G Stenkula, Helena A Jones, Karin Lindkvist-Petersson
Accumulating evidence suggests that dysregulated glycerol metabolism contributes to the pathophysiology of obesity and type 2 diabetes. Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Here, we propose a molecular mechanism where the AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation...
December 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27830474/simvastatin-rapidly-and-reversibly-inhibits-insulin-secretion-in-intact-single-islet-cultures
#18
Valentina Scattolini, Camilla Luni, Alessandro Zambon, Silvia Galvanin, Onelia Gagliano, Catalin Dacian Ciubotaru, Angelo Avogaro, Fabio Mammano, Nicola Elvassore, Gian Paolo Fadini
INTRODUCTION: Epidemiological studies suggest that statins may promote the development or exacerbation of diabetes, but whether this occurs through inhibition of insulin secretion is unclear. This lack of understanding is partly due to the cellular models used to explore this phenomenon (cell lines or pooled islets), which are non-physiologic and have limited clinical transferability. METHODS: Here, we study the effect of simvastatin on insulin secretion using single-islet cultures, an optimal compromise between biological observability and physiologic fidelity...
December 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27822337/on-the-anticataractogenic-effects-of-l-carnosine-is-it-best-described-as-an-antioxidant-metal-chelating-agent-or-glycation-inhibitor
#19
Hamdy Abdelkader, Michael Longman, Raid G Alany, Barbara Pierscionek
Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27810440/synthesis-and-structure-activity-relationships-of-glycine-amide-derivatives-as-novel-vascular-adhesion-protein-1-inhibitors
#20
Susumu Yamaki, Daisuke Suzuki, Jiro Fujiyasu, Masahiro Neya, Akira Nagashima, Mitsuhiro Kondo, Takafumi Akabane, Keitaro Kadono, Ayako Moritomo, Kosei Yoshihara
Vascular Adhesion Protein-1 (VAP-1) is a promising therapeutic target for the treatment of several inflammatory-related diseases including diabetic microvascular complication. We identified glycine amide derivative 3 as a novel structure with moderate VAP-1 inhibitory activity. Structure-activity relationship studies of glycine amide derivatives revealed that the tertiary amide moiety is important for stability in rat blood and that the position of substituents on the left phenyl ring plays an important role in VAP-1 inhibitory activity...
October 21, 2016: Bioorganic & Medicinal Chemistry
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