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https://www.readbyqxmd.com/read/29782963/bet-inhibition-by-jq1-alleviates-streptozotocin-induced-diabetic-cardiomyopathy
#1
Miao Guo, Hong-Xia Wang, Wen-Jun Chen
Diabetic cardiomyopathy is a cascade of complex events leading to eventual heart failure in diabetes. JQ1, one of Bromodomain and extra-terminal domain (BET) protein inhibitors, has exerted therapeutic effects on cancer proliferation, inflammation and cardiovascular disease. Recently, JQ1 was reported to protect mice from bleomycin-induced lung fibrosis and reverse the fibrotic response in carbon tetrachloride-induced liver fibrosis. However, its role in diabetic cardiomyopathy remains to be clarified. Our results indicated that JQ1 treatment suppressed cardiac fibrosis and improved cardiac function in a STZ-induced diabetic mouse model...
May 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29782207/the-benzodiazepine-anesthetic-midazolam-prevents-hyperglycemia-induced-microvascular-leakage-in-the-retinas-of-diabetic-mice
#2
Yeon-Ju Lee, Minsoo Kim, Jee-Yeon Lee, Se-Hui Jung, Hye-Yoon Jeon, Seung Ah Lee, Seongsik Kang, Eun-Taek Han, Won Sun Park, Seok-Ho Hong, Young-Myeong Kim, Kwon-Soo Ha
We investigated the beneficial effects of midazolam against vascular endothelial growth factor (VEGF)-induced vascular leakage and its molecular mechanism of action in human retinal endothelial cells (HRECs) and the retinas of diabetic mice. Midazolam inhibited VEGF-induced elevation of intracellular Ca2+ , generation of reactive oxygen species (ROS), and transglutaminase activation in HRECs; these effects were reversed by the GABA, type A (GABAA ) receptor antagonist flumazenil but not by the translocator protein antagonist PK11195...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29782007/intraportal-transplantation-of-pancreatic-islets-in-mouse-model
#3
Rahul Khatri, Birte Hussmann, Divya Rawat, Ali Osman Gürol, Thomas Linn
Pancreatic islet transplantation to reduce hyperglycemia is highly successful in rodents with chemically-induced diabetes. The most common transplantation site in experimental islet transplantation is the kidney capsule. However, as less is known about the interaction of pancreatic islets with blood constituents, it also makes sense to utilize the portal vein approach in experimental islet transplantation. This protocol demonstrates an intraportal islet transplantation technique in NMRI nude mice. Streptozotocin (180 mg/kg) is injected intraperitoneally to induce hyperglycemia in recipient mice...
May 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781726/in-vitro-analysis-of-glucose-and-quercetin-effects-on-m-tor-and-nrf-2-expression-in-hepg2-cell-line-diabetes-and-cancer-connection
#4
Amir Yarahmadi, Fatemeh Khademi, Zohreh Mostafavi-Pour, Fatemeh Zal
Some types of cancers show a strong relationship with diabetes and play a central role in mortality in the patient population suffering from diabetes mellitus. In this study, HepG2 cells have been used to investigate the toxic effects of hyperglycemia and/or quercetin (Q) on mammalian target of rapamycin (m-TOR) and nuclear factor erythroid 2-related factor 2 (Nrf-2) expression as central molecules involved in cancer. HepG2 cells were cultured with different concentrations of glucose (5.5, 30, and 50 mM) and/or Q (25 µM) for 48 and 72 h...
May 21, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29780554/mechanistic-perspective-and-functional-activity-of-insulin-in-amylin-aggregation
#5
Michal Baram, Sharon Gilead, Ehud Gazit, Yifat Miller
Insulin is a key regulatory polypeptide that is secreted from pancreatic β-cells and has several important effects on the synthesis of lipids, regulation of enzymatic activities, blood glucose levels and the prevention of hyperglycemia. Insulin was demonstrated to self-assemble into ordered amyloid fibrils upon repeated injections, although the possible biological significance of the supramolecular structures is enigmatic. Amylin is also an amyloidogenic polypeptide that is secreted from pancreatic β-cells and plays an important role in glycemic regulation preventing post-prandial spikes in blood glucose levels...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780390/dopaminergic-control-of-inflammation-and-glycemia-in-sepsis-and-diabetes
#6
Eleonora Feketeova, Zhifeng Li, Biju Joseph, Roshan Shah, Zoltan Spolarics, Luis Ulloa
Most preclinical treatments for sepsis failed in clinical trials in part because the experimental models of sepsis were performed on healthy animals that do not mimic septic patients. Here, we report that experimental diabetes worsens glycemia, inflammation, and mortality in experimental sepsis. Diabetes increases hyperglycemia, systemic inflammation, and mortality in sepsis. Diabetes exacerbates serum tumor necrosis factor (TNF) levels in sepsis by increasing splenic TNF production. Both serum from diabetic mice and glucose increase cytokine production in splenocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780142/diabetes-mellitus-induced-bone-fragility
#7
Ippei Kanazawa, Toshitsugu Sugimoto
Accumulating evidence has shown that the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM). Thus, DM-induced bone fragility has been recently recognized as a diabetic complication. Because the fracture risk is independent of the reduction in bone mineral density, deterioration of the bone quality may be the main cause of bone fragility. Although its mechanism remains poorly understood, accumulated collagen cross-links of advanced glycation end-products (AGEs) and dysfunctions of osteoblast and osteocyte may be involved...
May 18, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29778650/obesity-surgery-makes-patients-healthier-and-more-functional-real-world-results-from-the-united-kingdom-national-bariatric-surgery-registry
#8
Alexander Dimitri Miras, Kamocka Anna, Patel Darshan, Dexter Simon, Finlay Ian, Hopkins C James, Khan Omar, Reddy Marcus, Sedman Peter, Small Peter, Somers Shaw, Suzie Cro, Walton Peter, le Roux Carel W, Welbourn Richard
BACKGROUND: The National Bariatric Surgery Registry (NBSR) is the largest bespoke database in the field in the United Kingdom. OBJECTIVES: Our aim was to analyze the NBSR to determine whether the effects of obesity surgery on associated co-morbidities observed in small, randomized controlled clinical trials could be replicated in a "real life" setting within U.K. healthcare. SETTING: United Kingdom. METHODS: All NBSR entries for operations between 2000 and 2015 with associated demographic and co-morbidity data were analyzed retrospectively...
February 15, 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/29778648/impact-of-insulin-on-the-intestinal-microcirculation-in-a-model-of-sepsis-related-hyperglycemia
#9
Alexa Caldwell, Jan Niklas Morick, Anne-Marie Jentsch, Annette Wegener, Dragan Pavlovic, Nadia Al-Banna, Christian Lehmann
BACKGROUND: Sepsis involves dysfunctional glucose metabolism. Among patients with sepsis, hyperglycemia is frequent and insulin administration has been evaluated for glycemic control to improve patient outcomes. Only few studies have examined the hyperglycemic microcirculation and the impact of insulin on the microvasculature in sepsis. OBJECTIVE: To study the functional capillary density (FCD) and leukocyte activation within the intestinal microcirculation in endotoxin-induced experimental sepsis...
May 17, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29777522/impact-of-insulin-degludec-in-hospitalized-patients-with-and-without-type-2-diabetes-requiring-parenteral-enteral-nutrition-an-observational-study
#10
Giuseppe Fatati, Agnese Di Donato, Ilenia Grandone, Pina Menicocci, Eva Mirri, Giuseppe Prosperini, Marco Scardapane, Maria Chiara Rossi, Mariangela Palazzi
INTRODUCTION: Hyperglycemia in inpatients is a major problem, especially when nutritional support is required. This study aims to assess the impact of treatment with insulin degludec (IDeg) on mean blood glucose (BG) and glycemic variability in noncritical hospitalized patients with and without type 2 diabetes (T2DM) receiving enteral and/or parenteral nutrition (EN, PN). METHODS: Mean BG and glycemic variability from admission up to 7 days of hospitalization were evaluated in consecutive cases with and without T2DM...
May 17, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29777520/relationship-of-eating-patterns-and-metabolic-parameters-and-teneligliptin-treatment-interim-results-from-post-marketing-surveillance-in-japanese-type-2-diabetes-patients
#11
Takashi Kadowaki, Masakazu Haneda, Hiroshi Ito, Kazuyo Sasaki, Sonoe Hiraide, Miyuki Matsukawa, Makoto Ueno
INTRODUCTION: Healthy eating is a critical aspect of the prevention and management of type 2 diabetes (T2DM). Disrupted eating patterns can result in poor glucose control and increase the likelihood of diabetic complications. Teneligliptin inhibits dipeptidyl peptidase-4 activity for 24 h and suppresses postprandial hyperglycemia after all three daily meals. This interim analysis of data from the large-scale post-marketing surveillance of teneligliptin (RUBY) in Japan examined eating patterns and their relationship with metabolic parameters and diabetic complications...
May 17, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29777474/not-quite-type-1-or-type-2-what-now-review-of-monogenic-mitochondrial-and-syndromic-diabetes
#12
REVIEW
Roseanne O Yeung, Fady Hannah-Shmouni, Karen Niederhoffer, Mark A Walker
Diabetes mellitus is a heterogeneous group of conditions defined by resultant chronic hyperglycemia. Given the increasing prevalence of diabetes mellitus and the increasing understanding of genetic etiologies, we present a broad review of rare genetic forms of diabetes that have differing diagnostic and/or treatment implications from type 1 and type 2 diabetes. Advances in understanding the genotype-phenotype associations in these rare forms of diabetes offer clinically available examples of evolving precision medicine where defining the correct genetic etiology can radically alter treatment approaches...
May 18, 2018: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/29777362/the-silver-effect-of-admission-glucose-level-on-excellent-outcome-in-thrombolysed-stroke-patients
#13
Charlotte Rosso, Flore Baronnet, Belen Diaz, Raphael Le Bouc, Giulia Frasca Polara, Eric Jr Moulton, Sandrine Deltour, Anne Leger, Sophie Crozier, Yves Samson
Higher admission glucose levels (AGL) are associated with less favorable outcome in thrombolysis. But, could AGL's impact on outcome vary by onset-to-treatment (OTT) time? Is hyperglycemia associated with a shorter therapeutic time window for excellent outcome for thrombolysed stroke patients? We assessed predictive values of AGL, baseline NIHSS, age, and OTT time quartiles on excellent outcome (3-month modified Rankin score of 0-1) in 773 patients treated by rt-Pa. We added the AGL × OTT time quartile interaction in the model and separately analyzed the predictive values of AGL, age, and NIHSS for each OTT time quartile if the interaction was significant...
May 18, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29777212/regulation-of-macrophage-immunometabolism-in-atherosclerosis
#14
REVIEW
Graeme J Koelwyn, Emma M Corr, Ebru Erbay, Kathryn J Moore
After activation, cells of the myeloid lineage undergo robust metabolic transitions, as well as discrete epigenetic changes, that can dictate both ongoing and future inflammatory responses. In atherosclerosis, in which macrophages play central roles in the initiation, growth, and ultimately rupture of arterial plaques, altered metabolism is a key feature that dictates macrophage function and subsequent disease progression. This Review explores how factors central to the plaque microenvironment (for example, altered cholesterol metabolism, oxidative stress, hypoxia, apoptotic and necrotic cells, and hyperglycemia) shape the metabolic rewiring of macrophages in atherosclerosis as well as how these metabolic shifts in turn alter macrophage immune-effector and tissue-reparative functions...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29776987/mini-dose-glucagon-as-a-novel-approach-to-prevent-exercise-induced-hypoglycemia-in-type-1-diabetes
#15
Michael R Rickels, Stephanie N DuBose, Elena Toschi, Roy W Beck, Alandra S Verdejo, Howard Wolpert, Martin J Cummins, Brett Newswanger, Michael C Riddell
OBJECTIVE: Patients with type 1 diabetes who do aerobic exercise often experience a drop in blood glucose concentration that can result in hypoglycemia. Current approaches to prevent exercise-induced hypoglycemia include reduction in insulin dose or ingestion of carbohydrates, but these strategies may still result in hypoglycemia or hyperglycemia. We sought to determine whether mini-dose glucagon (MDG) given subcutaneously before exercise could prevent subsequent glucose lowering, and to compare the glycemic response to current approaches for mitigating exercise-associated hypoglycemia...
May 18, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29776406/the-effect-of-dpp-4-inhibition-to-improve-functional-outcome-after-stroke-is-mediated-by-the-sdf-1%C3%AE-cxcr4-pathway
#16
Fausto Chiazza, Harald Tammen, Hiranya Pintana, Grazyna Lietzau, Massimo Collino, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains...
May 19, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29775900/hordenine-protects-against-hyperglycemia-associated-renal-complications-in-streptozotocin-induced-diabetic-mice
#17
Shuhao Su, Meng Cao, Guangyuan Wu, Zi Long, Xiaodong Cheng, Junshu Fan, Zhongrui Xu, Hongfei Su, Yiming Hao, Ge Li, Jie Peng, Shuang Li, Xin Wang
The worldwide prevalence of diabetes and associated metabolic diseases has dramatically increased. Pharmacological treatment of diabetes is still limited. Hordenine (HOR), a phenethylamine alkaloid, is a natural constituent in many plants. The present study was designed to explore the possible anti-diabetic effect of HOR in streptozotocin (STZ)-induced diabetic mice. Combined treatment of HOR and insulin significantly reduced fasting and postprandial blood glucose level in diabetic mice. HOR and insulin did not show evident protective effect against structural and functional injuries of pancreas...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774650/outcomes-of-hyperglycemia-in-patients-with-and-without-diabetes-mellitus-hospitalized-for-infectious-diseases
#18
Amit Akirov, Talia Diker-Cohen, Hiba Masri-Iraqi, Hadar Duskin-Bitan, Ilan Shimon, Alexander Gorshtein
OBJECTIVE: Examine the prognostic implications of diabetes mellitus (DM) and the importance of glycemic control during hospitalization for infectious diseases. METHODS: Historical prospectively collected data of patients hospitalized between 2011-2013.Infection-related hospitalizations were classified according to site of infection. Median follow-up was 4.5 years. Outcome measures included in-hospital and end-of-follow-up mortality. RESULTS: The cohort included 8,051 patients (50% female, mean age ± SD, 68±20 years) with a primary diagnosis of an infectious disease...
May 17, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29774092/vorapaxar-treatment-reduces-mesangial-expansion-in-streptozotocin-induced-diabetic-nephropathy-in-mice
#19
Maaike Waasdorp, JanWillem Duitman, Sandrine Florquin, C Arnold Spek
Background: Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773993/diabetic-cardiomyopathy-impact-of-biological-sex-on-disease-development-and-molecular-signatures
#20
REVIEW
Ryan Toedebusch, Anthony Belenchia, Lakshmi Pulakat
Diabetic cardiomyopathy refers to a unique set of heart-specific pathological variables induced by hyperglycemia and insulin resistance. Given that cardiovascular disease (CVD) is the leading cause of death in the world, and type 2 diabetes incidence continues to rise, understanding the complex interplay between these two morbidities and developing novel therapeutic strategies is vital. Two hallmark characteristics specific to diabetic cardiomyopathy are diastolic dysfunction and cardiac structural mal-adaptations, arising from cardiac cellular responses to the complex toxicity induced by hyperglycemia with or without hyperinsulinemia...
2018: Frontiers in Physiology
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