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https://www.readbyqxmd.com/read/28342850/structural-basis-for-differential-activities-of-enantiomeric-ppar%C3%AE-agonists-binding-of-s35-to-the-alternate-site
#1
Jun Young Jang, Minseob Koh, Hwan Bae, Doo Ri An, Ha Na Im, Hyoun Sook Kim, Ji Young Yoon, Hye-Jin Yoon, Byung Woo Han, Seung Bum Park, Se Won Suh
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPARγ agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPARγ LBD; it is located beside the Ω loop between the helices H2' and H3...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342603/invited-review-the-anti-inflammatory-properties-of-dairy-lipids
#2
R Lordan, I Zabetakis
Dairy product consumption is often associated with negative effects because of its naturally high levels of saturated fatty acids. However, recent research has shown that dairy lipids possess putative bioactivity against chronic inflammation. Inflammation triggers the onset of several chronic diseases, including cardiovascular disease, type 2 diabetes mellitus, obesity, and cancer. This review discusses the anti-inflammatory properties of dairy lipids found in milk, yogurt, and cheese, and it examines them in relation to their implications for human health: their protective effects and their role in pathology...
March 22, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#3
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340010/non-proteinuric-rather-than-proteinuric-renal-diseases-are-the-leading-cause-of-end-stage-kidney-disease
#4
Davide Bolignano, Carmine Zoccali
Proteinuria is a distinguishing feature in primary and secondary forms of chronic glomerulonephritis, which contribute to no more than the 20% of the end-stage kidney disease (ESKD) population. The contribution of non-proteinuric nephropathies to the global ESKD burden is still poorly focused and scarce research efforts are dedicated to the elucidation of risk factors and mechanistic pathways triggering ESKD in these diseases. We abstracted information on proteinuria in the main renal diseases other than glomerulonephritides that may evolve into ESKD...
March 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28337686/telephone-delivered-behavioral-skills-intervention-for-african-american-adults-with-type-2-diabetes-a-randomized-controlled-trial
#5
Leonard E Egede, Joni S Williams, Delia C Voronca, Mulugeta Gebregziabher, Cheryl P Lynch
BACKGROUND: Diabetes disproportionately affects African Americans and is associated with poorer outcomes. Self-management is important for glycemic control; however, evidence in African Americans is limited. OBJECTIVE: To assess the efficacy of a combined telephone-delivered education and behavioral skills intervention (TBSI) in reducing hemoglobin A1c (HbA1c) levels in African Americans with type 2 diabetes, using a factorial design. DESIGN: This is a four-year randomized clinical trial, using a 2 x 2 factorial design...
March 23, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28335787/risk-factors-of-atherosclerotic-tissue-types-in-single-vessel-and-intermediate-coronary-lesions-a-cross-sectional-study
#6
Xianjin Wang, Qun Chen, Yu Xu, Yanqing Wang, Yang Yang, Ming Gu, Haihua Xu, Yanfang Zhao
BACKGROUND: Few data exist that correlate lesion-related risk factors such as conventional cardiovascular risks or lipoprotein-associated phospholipase A2 (Lp-PLA2) with tissue types within atherosclerotic plaques in patients with single-vessel and intermediate coronary lesions. METHODS: One hundred and ninety-two patients with single-vessel and intermediate coronary lesions were enrolled in a cross-sectional study and divided into two groups: stable angina pectoris (SAP) and acute coronary syndrome (ACS) groups...
March 23, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28335035/a-novel-cisd2-mutation-associated-with-a-classical-wolfram-syndrome-phenotype-alters-ca2-homeostasis-and-er-mitochondria-interactions
#7
Cécile Rouzier, David Moore, Cécile Delorme, Sandra Lacas-Gervais, Samira Ait-El-Mkadem, Konstantina Fragaki, Florence Burté, Valérie Serre, Sylvie Bannwarth, Annabelle Chaussenot, Martin Catala, Patrick Yu-Wai-Man, Véronique Paquis-Flucklinger
Wolfram syndrome (WS) is progressive neurodegenerative disease characterized by early-onset optic atrophy and diabetes mellitus, which can be associated with more extensive central nervous system and endocrine complications. The majority of patients harbour pathogenic WFS1 mutations, but recessive mutations in a second gene, CISD2, have been described in a small number of families with Wolfram syndrome type 2 (WFS2). The defining diagnostic criteria for WFS2 also consist of optic atrophy and diabetes mellitus, but unlike WFS1, this phenotypic subgroup has been associated with peptic ulcer disease and an increased bleeding tendency...
March 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334950/downstream-targets-of-gwas-detected-genes-for-breast-lung-and-prostate-and-colon-cancer-converge-to-g1-s-transition-pathway
#8
Olga Y Gorlova, Eugene I Demidenko, Christopher I Amos, Ivan P Gorlov
Genome-wide association studies (GWASs) identified over 500 single nucleotide polymorphisms (SNPs) influencing cancer risk. It is logical to expect the cancer-associated genes to cluster in pathways directly involved in carcinogenesis, e.g. cell cycle. Nevertheless, analyses of the GWAS-detected cancer risk genes usually show no or weak enrichment by known cancer genes.We hypothesized that GWAS-detected cancer risk-associated genes function as upstream regulators of the genes directly involved in carcinogenesis...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334637/on-the-non-linear-association-between-serum-uric-acid-levels-and-all-cause-mortality-rate-in-patients-with-type-2-diabetes-mellitus
#9
Olga Lamacchia, Andrea Fontana, Antonio Pacilli, Massimiliano Copetti, Stefania Fariello, Monia Garofolo, Giuseppe Penno, Vincenzo Trischitta, Salvatore De Cosmo, Mauro Cignarelli
BACKGROUND AND AIMS: High levels of serum uric acid (SUA) are associated with increased mortality risk in the general population. Contrasting results are available in people with diabetes. The aim of our study was to investigate the association and its functional form between SUA and all cause-mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: We studied three cohorts of patients with T2DM: Gargano Mortality Study, Foggia Mortality Study, Pisa Mortality Study...
March 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28332327/restless-legs-syndrome-willis-ekbom-disease-in-type-2-diabetes-as-the-initial-manifestation-of-parkinson-s-disease-and-major-cardiovascular-disease
#10
Chun-Hsien Hsu, Shu-Man Yu, Shu Chuen Lau, Yen-Lin Chen, Dee Pei, I-Chao Liu
No abstract text is available yet for this article.
March 23, 2017: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/28332144/efficacy-and-safety-of-ideglira-in-participants-with-type-2-diabetes-in-india-uncontrolled-on-oral-antidiabetic-drugs-and-basal-insulin-data-from-the-dual-clinical-trial-program
#11
Kamlesh Khunti, Viswanathan Mohan, Sunil M Jain, Trine Welløv Boesgaard, Kamilla Begtrup, Bipin Sethi
INTRODUCTION: The efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II...
March 22, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#12
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28327848/-mesenchymal-stem-cells-definitions-culture-and-potential-applications
#13
Willy Ceron, Iván Lozada-Requena, Kiomi Ventocilla, Sandra Jara, Milagros Pinto, Marco Cabello, José L Aguilar
In recent years, mesenchymal stem cells (MSC) have become very important due to their high plasticity and their ability to release paracrine factors able to interact with various cell types, tissues and organs. The use of MSC in regenerative medicine became of vital importance, since they do not express histocompatibility MHC molecules class II nor costimulant molecules, and low expression of MHC class I, will not be rejected by individuals of same species, they could be used in an autologous, and eventually, allogeneic manner...
October 2016: Revista Peruana de Medicina Experimental y Salud Pública
https://www.readbyqxmd.com/read/28326749/a-case-of-autoimmune-polyendocrine-syndrome-type-i-with-strong-positive-gad-antibody-titer-followed-up-with-glucose-tolerance-measured-by-oral-glucose-tolerance-test
#14
Rie Murakami, Toshihide Kawai, Shu Meguro, Matsuhiko Hayashi, Hiroshi Itoh
A 26-year-old Japanese woman presented with adrenal insufficiency, and treatment was started with cortisone and fludrocortisone in 1975. A few years later, she presented with hypoparathyroidism and was diagnosed with autoimmune polyendocrine syndrome type I (APS I), and treatment with calcium and alfacalcidol was started. She was found to have subacute thyroiditis and relative adrenal failure in 2006. Her condition remained stable under treatment with cortisone, fludrocortisone, levothyroxine, calcium lactate, precipitated calcium carbonate and alfacalcidol...
January 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28325801/insulin-and-glucagon-like-peptide-1-receptor-agonist-combination-therapy-in-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#15
REVIEW
Maria Ida Maiorino, Paolo Chiodini, Giuseppe Bellastella, Annalisa Capuano, Katherine Esposito, Dario Giugliano
OBJECTIVE: The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28325698/factors-associated-with-antidiabetic-medication-non-adherence-in-patients-with-incident-comorbid-depression
#16
Carlotta Lunghi, Arsène Zongo, Jocelyne Moisan, Jean-Pierre Grégoire, Line Guénette
AIM: To identify factors associated with antidiabetic drug (AD) non-adherence among patients with type 2 diabetes and depression. STUDY DESIGN AND SETTINGS: We conducted a population-based retrospective cohort study among new AD users with a diagnosis of depression following AD initiation. We used public health insurance data from Quebec. The dependent variable was non-adherence (i.e., <90% of days covered by ≥1AD) in the year after a depression diagnosis. Different sociodemographic, clinical and medication-related variables were assessed as potential factors of non-adherence to AD treatment...
March 12, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28324049/piloting-a-remission-strategy-in-type-2-diabetes-results-of-a-randomized-controlled-trial
#17
Natalia McInnes, Ada Smith, Rose Otto, Jeffrey Vandermey, Zubin Punthakee, Diana Sherifali, Kumar Balasubramanian, Stephanie Hall, Hertzel C Gerstein
Context: Medical strategies targeting remission of type 2 diabetes have not been systematically studied. Objective: This trial assessed the feasibility, safety and potential to induce remission of a short-term intensive metabolic strategy. Design: A randomized, parallel, open-label pilot trial in 83 participants followed for 52 weeks. Setting: Ambulatory care. Participants: Patients with type 2 diabetes of up to 3 years in duration...
March 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324038/efficacy-of-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-t2dm-patients-with-very-high-hba1c
#18
Muhammad Abdul-Ghani, Osama Mujahid, Ayman Mujahid, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
Aim: To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in poorly controlled type 2 diabetic patients with very high HbA1c (HbA1c>10%) on metformin plus sulfonylurea and long duration of disease. Research Design and Methods: 101 participants in Qatar Study with very poor glycemic control (HbA1c > 10%) and long duration of diabetes (10.9 years) on maximum/near-maximum doses of sulfonylurea plus metformin were randomized to receive: (i) pioglitazone plus weekly exenatide (Combination Therapy), or (ii) basal plus prandial insulin (Insulin Therapy) to maintain HbA1c <7...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323921/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#19
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs, non-coding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
February 17, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28323911/monogenic-diabetes-accounts-for-6-3-of-cases-referred-to-15-italian-pediatric-diabetes-centers-during-2007-2012
#20
Maurizio Delvecchio, Enza Mozzillo, Giuseppina Salzano, Dario Iafusco, Giulio Frontino, Patrizia I Patera, Ivana Rabbone, Valentino Cherubini, Valeria Grasso, Nadia Tinto, Sabrina Giglio, Giovanna Contreas, Rosa Di Paola, Alessandro Salina, Vittoria Cauvin, Stefano Tumini, Giuseppe d'Annunzio, Lorenzo Iughetti, Vilma Mantovani, Giulio Maltoni, Sonia Toni, Marco Marigliano, Fabrizio Barbetti
Context: Etiologic diagnosis of diabetes may impact on therapeutic strategy, and prognosis of chronic complications. Objective: The aim of the study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers, and the influence of etiologic diagnosis on therapy. Design, Setting and Patients: This was a retrospective study. Clinical records of 3781 consecutive patients (age: 0-18 years) referred to fifteen pediatric diabetes clinics and diagnosed with diabetes or IFG between Jan/1/2007 and Dec/31/2012 were examined...
February 16, 2017: Journal of Clinical Endocrinology and Metabolism
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