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https://www.readbyqxmd.com/read/28097011/a-selective-gpr40-ffar1-agonist-ly2881835-provides-immediate-and-durable-glucose-control-in-rodent-models-of-type-2-diabetes
#1
Yanyun Chen, Min Song, Jonathan P Riley, Charlie C Hu, Xianbu Peng, Donalyn Scheuner, Krister Bokvist, Pranab Maiti, Steven D Kahl, Chahrzad Montrose-Rafizadeh, Chafiq Hamdouchi, Anne Reifel Miller
LY2881835 is a selective, potent, and efficacious GPR40 agonist. The objective of the studies described here was to examine the pharmacological properties of LY2881835 in preclinical models of T2D. Significant increases in insulin secretion were detected when LY2881835 was tested in primary islets from WT mice but not in islets from GPR40 KO mice. Furthermore, LY2881835 potentiated glucose stimulated insulin secretion in normal lean mice. Acute administration of LY2881835 lowered glucose during OGTTs in WT mice but not in GPR40 KO mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#2
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28073315/metabolically-active-3-dimensional-brown-adipose-tissue-engineered-from-white-adipose-derived-stem-cells
#3
Jessica P Yang, Amy Elizabeth Anderson, Annemarie McCartney, Xavier Ory, Garret Ma, Elisa Pappalardo, Joel Bader, Jennifer Elisseeff
Brown adipose tissue (BAT) has a unique capacity to expend calories by decoupling energy expenditure from ATP production, therefore BAT could realize therapeutic potential to treat metabolic diseases such as obesity and type 2 diabetes. Recent studies have investigated markers and function of native BAT, however, successful therapies will rely on methods that supplement the small existing pool of brown adipocytes in adult humans. In this study, we engineered BAT from both human and rat adipose precursors and determined whether these ex vivo constructs could mimic in vivo tissue form and metabolic function...
January 10, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28067255/serelaxin-treatment-reverses-vascular-dysfunction-and-left-ventricular-hypertrophy-in-a-mouse-model-of-type-1-diabetes
#4
Hooi Hooi Ng, Chen Huei Leo, Darnel Prakoso, Chengxue Qin, Rebecca H Ritchie, Laura J Parry
Serelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28046026/comparison-of-in-vitro-and-ex-vivo-wound-healing-assays-for-the-investigation-of-diabetic-wound-healing-and-demonstration-of-a-beneficial-effect-of-a-triterpene-extract
#5
Christopher Ueck, Thomas Volksdorf, Pia Houdek, Sabine Vidal-Y-Sy, Susanne Sehner, Bernhard Ellinger, Ralf Lobmann, Axel Larena-Avellaneda, Konrad Reinshagen, Ina Ridderbusch, Klaas Kohrmeyer, Ingrid Moll, Rolf Daniels, Philipp Werner, Irmgard Merfort, Johanna M Brandner
Diabetes mellitus is a frequent cause for chronic, difficult-to-treat wounds. New therapies for diabetic wounds are urgently needed and in-vitro or ex-vivo test systems are essential for the initial identification of new active molecules. The aim of this study is to compare in-vitro and ex-vivo test systems for their usability for early drug screening and to investigate the efficacy of a birch bark triterpene extract (TE) that has been proven ex-vivo and clinically to accelerate non-diabetic wound healing (WH), in a diabetic context...
2017: PloS One
https://www.readbyqxmd.com/read/28045060/soluble-ox40l-and-jag1-induce-selective-proliferation-of-functional-regulatory-t-cells-independent-of-canonical-tcr-signaling
#6
Prabhakaran Kumar, Khaled Alharshawi, Palash Bhattacharya, Alejandra Marinelarena, Christine Haddad, Zuoming Sun, Shigeru Chiba, Alan L Epstein, Bellur S Prabhakar
Regulatory T-cells (Tregs) play a pivotal role in maintaining peripheral tolerance. Increasing Treg numbers/functions has been shown to ameliorate autoimmune diseases. However, common Treg expansion approaches use T-Cell Receptor (TCR)-mediated stimulation which also causes proliferation of effector T-cells (Teff). To overcome this limitation, purified patient-specific Tregs are expanded ex vivo and transfused. Although promising, this approach is not suitable for routine clinical use. Therefore, an alternative approach to selectively expand functional Tregs in vivo is highly desired...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28038946/hmgb1-modulation-in-pancreatic-islets-using-a-cell-permeable-a-box-fragment
#7
Yong Hwa Hwang, Min Jun Kim, Yong-Kyu Lee, Minhyung Lee, Dong Yun Lee
Although pancreatic islet implantation is an attractive strategy for curing diabetes mellitus, implanted cells are immunologically eliminated due to early islet graft loss. One of main issues in early islet graft loss is the secretion of high-mobility group-box-1 (HMGB1) protein from the damaged islet cells, which is known as a cytokine-like factor. Therefore, regulating the activity of HMGB1 protein offers an alternative strategy for improving outcomes of islet cell therapy. To this end, we first demonstrated that HMGB1 protein could be bound to its A-box fragment (HMGB1 A-box) with higher binding affinity, resembling anti-HMGB1 antibody...
December 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28027880/1-4-anhydro-4-seleno-d-talitol-setal-protects-endothelial-function-in-the-mouse-aorta-by-scavenging-superoxide-radicals-under-conditions-of-acute-oxidative-stress
#8
Hooi Hooi Ng, Chen Huei Leo, Kelly O'Sullivan, Stefanie-Ann Alexander, Michael J Davies, Carl H Schiesser, Laura J Parry
Hyperglycaemia increases the generation of reactive oxidants in blood vessels and is a major cause of endothelial dysfunction. A water-soluble selenium-containing sugar (1,4-Anhydro-4-seleno-D-talitol, SeTal) has potent antioxidant activity in vitro and is a promising treatment to accelerate wound healing in diabetic mice. One possible mechanism of SeTal action is a direct effect on blood vessels. Therefore, we tested the hypothesis that SeTal prevents endothelial dysfunction by scavenging reactive oxidants in isolated mouse aorta under conditions of acute oxidative stress induced by hyperglycaemia...
December 24, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28011992/appl1-prevents-pancreatic-beta-cell-death-and-inflammation-by-dampening-nf%C3%AE%C2%BAb-activation-in-a-mouse-model-of-type-1-diabetes
#9
Xue Jiang, Yawen Zhou, Kelvin K L Wu, Zhanrui Chen, Aimin Xu, Kenneth K Y Cheng
AIMS/HYPOTHESIS: Beta cell inflammation and demise is a feature of type 1 diabetes. The insulin-sensitising molecule 'adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1' (APPL1), which contains an NH2-terminal Bin/Amphiphysin/Rvs domain, a central pleckstrin homology domain and a COOH-terminal phosphotyrosine-binding domain, has been shown to modulate inflammatory response in various cell types but its role in regulating beta cell mass and inflammation in type 1 diabetes remains unknown...
December 23, 2016: Diabetologia
https://www.readbyqxmd.com/read/28006837/joint-associations-of-smoking-and-television-viewing-time-on-cancer-and-cardiovascular-disease-mortality
#10
Megan S Grace, Brigid M Lynch, Francis Dillon, Elizabeth L M Barr, Neville Owen, David W Dunstan
Excessive sitting time and smoking are pro-inflammatory lifestyle factors that are associated with both cancer and cardiovascular disease (CVD) mortality. However, their joint associations have not been investigated. We examined the associations of television (TV) viewing time with cancer and CVD mortality, according to smoking status, among 7,498 non-smokers (34% ex-smokers) and 1,409 current-smokers in the Australian Diabetes, Obesity and Lifestyle Study. During 117,506 person-years (median 13.6 years) of follow-up, there were 346 cancer and 209 CVD-related deaths...
December 22, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27996320/mitigating-reductions-in-glucose-during-exercise-on-closed-loop-insulin-delivery-the-ex-snacks-study
#11
Neha S Patel, Michelle A Van Name, Eda Cengiz, Lori R Carria, Eileen M Tichy, Kate Weyman, Stuart A Weinzimer, William V Tamborlane, Jennifer L Sherr
OBJECTIVE: To assess whether snacking could be used with closed-loop (CL) insulin delivery to avoid exercise-induced reductions in plasma glucose (PG), as well as elevations in PG at the end of exercise. RESEARCH DESIGN AND METHODS: Twelve type 1 diabetes (T1D) subjects (age 13-36 years, duration 10.7 ± 8.4 years, A1c 7.4% ± 0.8% [57 ± 8.7 mmol/mol]) underwent two 105-min exercise studies while under CL control: CL alone and CL+snack. Exercise, commenced at 3 PM, consisted of four 15-min periods of brisk treadmill walking to 65%-70% HRmax (separated by three 5-min rest periods), followed by a 30-min recovery period...
December 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27994379/preoperative-red-cell-distribution-width-not-a-useful-prognostic-indicator-for-30-day-mortality-in-patients-who-undergo-major-or-ultra-major-noncardiac-surgery
#12
Yik-Nang Cheung, Hoi-Ping Shum, King-Chung Chan, Wing-Wa Yan
BACKGROUND: Red cell distribution width (RDW) has been shown to be associated with mortality in cardiac surgical patients. This study investigates the association of RDW with the 30-day mortality for those patients who undergo major- or ultra-major noncardiac surgery. METHODS: Patients who received major- or ultra-major noncardiac surgery between July 2012 and May 2013 were included in the study and patients those with preoperative hemoglobin <10 g/day were excluded from the study...
November 2016: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/27990144/glucose-regulated-protein-78-induced-myeloid-antigen-presenting-cells-maintained-tolerogenic-signature-upon-lps-stimulation
#13
Muyang Yang, Fan Zhang, Kai Qin, Min Wu, Heli Li, Huifen Zhu, Qin Ning, Ping Lei, Guanxin Shen
The 78-kDa glucose-regulated protein (Grp78) is stress-inducible chaperone that mostly reside in the endoplasmic reticulum. Grp78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. As antigen-presenting cells (APCs) play a critical role in both the priming of adaptive immune responses and the induction of self-tolerance, herein, we investigated the effect of Grp78 on the maturation of murine myeloid APCs (CD11c(+) cells)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27981357/overexpression-of-protein-kinase-stk25-in-mice-exacerbates-ectopic-lipid-accumulation-mitochondrial-dysfunction-and-insulin-resistance-in-skeletal-muscle
#14
Urszula Chursa, Esther Nuñez-Durán, Emmelie Cansby, Manoj Amrutkar, Silva Sütt, Marcus Ståhlman, Britt-Marie Olsson, Jan Borén, Maria E Johansson, Fredrik Bäckhed, Bengt R Johansson, Carina Sihlbom, Margit Mahlapuu
AIMS/HYPOTHESIS: Understanding the molecular networks controlling ectopic lipid deposition and insulin responsiveness in skeletal muscle is essential for developing new strategies to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis. Here, we assessed the role of STK25 in control of ectopic fat storage and insulin responsiveness in skeletal muscle...
December 16, 2016: Diabetologia
https://www.readbyqxmd.com/read/27933093/long-term-consumption-of-an-obesogenic-high-fat-diet-prior-to-ischemia-reperfusion-mediates-cardioprotection-via-epac1-dependent-signaling
#15
F Edland, A Wergeland, R Kopperud, K S Åsrud, E A Hoivik, S L Witsø, R Æsøy, L Madsen, K Kristiansen, M Bakke, S O Døskeland, A K Jonassen
BACKGROUND: Obesity is still considered a risk factor for cardiovascular disease, although more recent knowledge also suggests obesity to be associated with reduced morbidity and mortality - the "obesity paradox". This study explores if long-term feeding of an obesogenic high fat diet renders the myocardium less susceptible to ischemic-reperfusion induced injury via Epac-dependent signaling. METHODS: Wild type (wt), Epac1 (Epac1(-/-)) and Epac2 (Epac2(-/-)) deficient mice were fed a high fat (HFD) or normal chow diet (ND) for 33 ± 1 weeks...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27932675/the-effects-of-voluntary-exercise-and-prazosin-on-capillary-rarefaction-and-metabolism-in-streptozotocin-induced-diabetic-male-rats
#16
Emily C Dunford, Erwan Leclair, Julian Aiken, Erin R Mandel, Tara L Haas, Olivier Birot, Michael C Riddell
Type-1 diabetes mellitus (T1D) causes impairments within the skeletal muscle microvasculature. Both regular exercise and prazosin have been shown to improve skeletal muscle capillarization and metabolism in healthy rats, through distinct angiogenic mechanisms. The aim of this study was to evaluate the independent and additive effects of voluntary exercise and prazosin treatment on capillary-to-fiber ratio (C:F) in streptozotocin (STZ)-treated diabetic rats. STZ (65mg/kg) was intraperitoneally administered to male Sprague-Dawley rats (n=36) to induce diabetes, with healthy, non-diabetic, sedentary rats (n=10) as controls...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27919931/low-mt-co1-in-monocytes-and-microvesicles-is-associated-with-outcome-in-patients-with-coronary-artery-disease
#17
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
#18
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
#19
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
#20
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
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