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Pioglitazon

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https://www.readbyqxmd.com/read/28716729/study-of-new-interactions-of-glitazone-s-stereoisomers-and-the-endogenous-ligand-15d-pgj2-on-six-different-ppar-gamma-proteins
#1
Samuel Álvarez-Almazán, Martiniano Bello, Feliciano Tamay-Cach, Marlet Martínez-Archundia, Diana Alemán-González-Duhart, José Correa-Basurto, Jessica Elena Mendieta-Wejebe
Diabetes mellitus is a chronic disease characterized by hyperglycemia, insulin resistance and hyperlipidemia. Glitazones or thiazolidinediones (TZD) are drugs that act as insulin-sensitizing agents whose molecular target is the peroxisome proliferator-activated receptor gamma (PPARγ). The euglycemic action of TZD has been linked with the induction of type 4 glucose transporter. However, it has been shown that the effect of TZD depends on the specific stereoisomer that interacts with PPARγ. Therefore, this work is focused on exploring the interactions and geometry adopted by glitazone's stereoisomers and one endogenous ligand on different conformations of the six crystals of the PPARγ protein using molecular docking and molecular dynamics (MD) simulations accompanied by the MMGBSA approach...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28716464/modulating-effects-of-omega-3-fatty-acids-and-pioglitazone-combination-on-insulin-resistance-through-toll-like-receptor-4-in-type-2-diabetes-mellitus
#2
Salma M Eraky, Noha Abdel-Rahman, Laila A Eissa
Toll-like receptor 4 (TLR-4) plays important roles in innate immunity. Changes in the reduction-oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance. An action thought to be mediated by TLRs. Omega-3 fatty acids and Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) agonists as pioglitazone are used for decreasing inflammation. The aim of this study is to investigate the anti-diabetic effects of combining omega -3 fatty acid with pioglitazone on type 2 diabetes, and the modifying effects on TLR-4...
June 17, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28714405/emerging-targets-to-relieve-fat-stress-induced-liver-diseases-udca-tocotrienol-%C3%AF-3-pufas-and-igy-targeted-npc1l1-cholesterol-transporter
#3
Ji-Young Cha, Jong-Min Park, Ho-Jae Lee, Jin-Sik Bae, Young-Min Han, Byung-Chul Oh, Kwang Hyun Ko, Ki-Baik Hahm
Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to non-alcoholic steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28712591/normalizing-ovulation-rate-by-preferential-reduction-of-hepato-visceral-fat-in-adolescent-girls-with-polycystic-ovary-syndrome
#4
Lourdes Ibáñez, Luis Del Río, Marta Díaz, Giorgia Sebastiani, Óscar J Pozo, Abel López-Bermejo, Francis de Zegher
PURPOSE: Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment. METHODS: This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23...
July 13, 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/28708885/pioglitazone-ameliorates-glomerular-nlrp3-inflammasome-activation-in-apolipoprotein-e-knockout-mice-with-diabetes-mellitus
#5
Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan
OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO...
2017: PloS One
https://www.readbyqxmd.com/read/28706330/effects-of-co-treatment-with-pioglitazone-and-methotrexate-on-experimentally-induced-rheumatoid-arthritis-in-wistar-albino-rats
#6
Tanushree Roy, Indranil Banerjee, Saikat Ghosh, Ranjita Santra Dhali, Anuradha De Pati, Santanu Kumar Tripathi
OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28705172/endocannabinoid-receptor-blockade-reduces-alanine-aminotransferase-in-polycystic-ovary-syndrome-independent-of-weight-loss
#7
Alison J Dawson, Eric S Kilpatrick, Anne-Marie Coady, Abeer M M Elshewehy, Youssra Dakroury, Lina Ahmed, Stephen L Atkin, Thozhukat Sathyapalan
BACKGROUND: Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. METHODS: Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od)...
July 14, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28698283/long-term-rates-of-mitochondrial-protein-synthesis-are-increased-in-mouse-skeletal-muscle-with-high-fat-feeding-regardless-of-insulin-sensitizing-treatment
#8
Sean A Newsom, Benjamin F Miller, Karyn L Hamilton, Sarah E Ehrlicher, Harrison D Stierwalt, Matthew M Robinson
Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet, the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28694481/mechanisms-underlying-neuro-inflammation-and-neurodevelopmental-toxicity-in-the-mouse-neocortex-following-prenatal-exposure-to-ethanol
#9
Munekazu Komada, Nao Hara, Satoko Kawachi, Kota Kawachi, Nao Kagawa, Tetsuji Nagao, Yayoi Ikeda
Fetal alcohol spectrum disorders (FASD) constitute a wide range of disorders that arise from prenatal exposure to ethanol (EtOH). However, detailed reports regarding the adverse effects of prenatal EtOH exposure on neocortical morphology and its underlying pathogenic mechanisms are limited. In the present study, we aimed to characterize the anatomical abnormalities of neocortical development and their correlation with microglial properties and neuro-inflammation in a mouse model of FASD. We evaluated the development and maturation of the neocortex in ICR mice prenatally exposed to 25% (w/v) EtOH using histological and molecular analyses...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28685513/effects-of-vildagliptin-or-pioglitazone-on-glycemic-variability-and-oxidative-stress-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-monotherapy-a-16-week-randomised-open-label-pilot-study
#10
Nam Hoon Kim, Dong Lim Kim, Kyeong Jin Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim
BACKGROUND: Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes. METHODS: In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17) or pioglitazone (15 mg once daily, n=14) treatment groups for 16 weeks...
June 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28683454/interactions-of-tlr4-and-ppar%C3%AE-dependent-on-ampk-signalling-pathway-contribute-to-anti-inflammatory-effects-of-vaccariae-hypaphorine-in-endothelial-cells
#11
Haijian Sun, Xuexue Zhu, Wei Lin, Yuetao Zhou, Weiwei Cai, Liying Qiu
Background /Aims: Accumulating evidence indicates that endothelial inflammation is one of the critical determinants in pathogenesis of atherosclerotic cardiovascular disease. Our previous studies had demonstrated that Vaccariae prevented high glucose or oxidative stress-triggered endothelial dysfunction in vitro. Very little is known about the potential effects of hypaphorine from Vaccariae seed on inflammatory response in endothelial cells. METHODS: In the present study, we evaluated the anti-inflammatory effects of Vaccariae hypaphorine (VH) on lipopolysaccharide (LPS)-challenged endothelial EA...
July 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28683300/three-year-data-from-5-harmony-phase-3-clinical-trials-of-albiglutide-in-type-2-diabetes-mellitus-long-term-efficacy-with-or-without-rescue-therapy
#12
Philip D Home, Bo Ahrén, Jane E B Reusch, Marc Rendell, Peter N Weissman, Deborah T Cirkel, Diane Miller, Philip Ambery, Molly C Carr, Michael A Nauck
AIMS: Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period. METHODS: Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or placebo across a spectrum of clinical care, lasted for a preplanned 3years. Participants with uncontrolled hyperglycaemia who met predetermined criteria could receive rescue medication...
June 15, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28680569/ppar%C3%AE-attenuates-hypoxia-induced-hypertrophic-transcriptional-pathways-in-the-heart
#13
Abubakr Chaudhry, Kristal A Carthan, Bum-Yong Kang, John Calvert, Roy L Sutliff, C Michael Hart
Chronic hypoxia-induced pulmonary hypertension (PH) is characterized by increased pressure and resistance in the pulmonary vasculature and hypertrophy of the right ventricle (RV). The transcription factors, nuclear factor activated T-cells (NFAT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB/p65) contribute to RV hypertrophy (RVH). Because peroxisome proliferator-activated receptor gamma (PPARγ) activation attenuates hypoxia-induced PH and RVH, we hypothesized that PPARγ inhibits activation of RV hypertrophic transcriptional signaling mechanisms...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28679956/pioglitazone-mediated-reversal-of-elevated-glucose-metabolism-in-the-airway-epithelium-of-mouse-lung-adenocarcinomas
#14
Donghai Xiong, Jing Pan, Qi Zhang, Eva Szabo, Mark Steven Miller, Ronald A Lubet, Yian Wang, Ming You
Airway epithelial cells are prone to the damage caused by lung cancer risk factors, such as cigarette smoking. Little is known about surrogate biomarkers in the bronchial airway epithelium that can be used to assess the effect of potential chemoprevention drugs on lung adenocarcinoma formation/progression. Pioglitazone has been suggested as a chemoprevention drug for lung cancer. To study the mechanisms underlying the role of pioglitazone in lung cancer prevention, we performed transcriptome sequencing (RNA-Seq) and found that Kras signaling was repressed by pioglitazone treatment in the airway epithelial cells of mice with lung adenocarcinoma (FDR q = 9...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28677333/review-article-new-treatments-in-non-alcoholic-fatty-liver-disease
#15
REVIEW
S A Townsend, P N Newsome
BACKGROUND: Non-alcoholic fatty liver disease is the fastest growing cause of liver disease in the Western world, yet there is no approved pharmacotherapy. While lifestyle modifications remain the mainstay of treatment, only a proportion of individuals are able to make or sustain them, and so more treatment options are required. AIM: To review the potential benefit of drugs used in clinical practice, those entering phase II trials, and compounds being investigated in pre-clinical studies...
July 4, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28676020/current-and-potential-future-pharmacological-approaches-for-non-alcoholic-fatty-liver-disease
#16
Konstantinos Imprialos, Konstantinos Stavropoulos, Sofia Bouloukou, Georgios Kerpiniotis, Asterios Karagiannis, Michael Doumas
BACKGOUND: Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the general population. The disease ranges from simple steatosis, to non-alcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. Several drugs are used in daily clinical practice to manage the disease. However, data on their efficacy in liver histology are not consistent. AIM: We discuss current treatment options for NAFLD and NASH and preliminary results from novel drugs under investigation...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28676019/statins-an-under-appreciated-asset-for-the-prevention-and-the-treatment-of-nafld-or-nash-and-the-related-cardiovascular-risk
#17
Vasilios G Athyros, Chrysa Boutari, Konstantinos Stavropoulos, Panagiotis Anagnostis, Konstantinos P Imprialos, Michael Doumas, Asterios Karagiannis
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease (30% of the general population) and up to 40% of cases advance to the more severe form of the disease: non-alcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD). There is no generally accepted effective treatment for NAFLD/NASH. The joint guidelines of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) suggest the "off label" use of pioglitazone in patients without type 2 diabetes mellitus (T2DM) and pioglitazone in subjects with T2DM or vitamin E or their combination for the treatment of NASH; however pioglitazone has considerable limitations: weight gain, bone fractures in women, and heart failure...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28676018/can-serum-uric-acid-lowering-therapy-contribute-to-the-prevention-or-treatment-of-nonalcoholic-fatty-liver-disease
#18
Paschalis Paschos, Vasilios G Athyros, Achilleas Tsimperidis, Anastasia Katsoula, Nikolaos Grammatikos, Olga Giouleme
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries with potential progression to nonalcoholic steatohepatitis (NASH) and cirrhosis, is associated with cardiovascular disease (CVD) mortality. Several studies have reported a relationship between uric acid and NAFLD/NASH and it seems that serum uric acid (SUA) is a significant independent factor for the development of NAFLD. Potential mediating mechanisms include insulin resistance, endothelial dysfunction, and activation of inflammasome, especially NLRP3...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28674957/a-review-of-the-long-term-efficacy-tolerability-and-safety-of-exenatide-once-weekly-for-type-2-diabetes
#19
REVIEW
Stefano Genovese, Edoardo Mannucci, Antonio Ceriello
INTRODUCTION: Exenatide once weekly (ExeOW, Bydureon(®), Astra Zeneca), a drug belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists, is the first agent approved for treatment of type 2 diabetes (T2D) that can be administered on a weekly basis. METHODS: Data concerning treatment of T2D with ExeOW are reviewed with special reference to its long-term efficacy, tolerability, and safety. Relevant literature was identified through the PubMed database from inception to January 2015...
July 3, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28665544/pioglitazone-attenuates-atrial-remodeling-and-vulnerability-to-atrial-fibrillation-in-alloxan-induced-diabetic-rabbits
#20
Changle Liu, Ruimeng Liu, Huaying Fu, Jian Li, Xinghua Wang, Lijun Cheng, Panagiotis Korantzopoulos, Gary Tse, Guangping Li, Tong Liu
BACKGROUND/AIMS: Recent evidence indicates that peroxisome proliferator-activated receptor (PPAR)-γ activators exert anti-inflammatory and anti-oxidant actions. However, the underlying mechanisms by which these agents prevent atrial remodeling in diabetes are not completely elucidated. We sought to investigate the potential effects of pioglitazone, a PPAR-γ activator, on atrial remodeling and atrial fibrillation (AF) inducibility in diabetic rabbits. METHODS: Alloxan-induced diabetic rabbits were randomly divided into three groups: diabetes only, diabetes treated with low-dose pioglitazone (4 mg/day/kg), or diabetes treated with high dose pioglitazone (8 mg/day/kg) (n = 24 for each group)...
June 30, 2017: Cardiovascular Therapeutics
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