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https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#1
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/28339962/fstl3-is-increased-in-renal-dysfunction
#2
Susan Kralisch, Annett Hoffmann, Nora Klöting, Anette Bachmann, Jürgen Kratzsch, Jens-Uwe Stolzenburg, Anja Dietel, Joachim Beige, Matthias Anders, Ingolf Bast, Matthias Blüher, Ming-Zhi Zhang, Raymond C Harris, Michael Stumvoll, Mathias Fasshauer, Thomas Ebert
Background.: Follistatin-like 3 (FSTL3) is a novel cytokine that regulates insulin sensitivity and counteracts activin/myostatin signalling. In the present study, regulation of FSTL3 in renal dysfunction was investigated in both human chronic kidney disease (CKD) and acute kidney dysfunction (AKD). Furthermore, mFSTL3 expression was analysed in insulin-sensitive tissues in a mouse model of CKD. Methods.: Circulating FSTL3 was quantified by enzyme-linked immunosorbent assay in 581 patients with CKD covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5...
March 3, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339345/alanine-aminotransferase-is-a-marker-of-lipotoxicity-consequences-and-hyperandrogenemia-in-women-with-polycystic-ovary-syndrome
#3
Matea Belan, Chloé Pelletier, Jean-Patrice Baillargeon
BACKGROUND: Several studies have reported higher levels of Alanine aminotransferase (ALT) in women with polycystic ovary syndrome (PCOS) compared with control subjects. Plasma ALT levels are considered a marker of hepatic lipotoxicity because of their significant associations with different hepatic metabolic dysfunctions, such as hepatic steatosis and hepatic insulin resistance. METHODS: Retrospective chart review aiming to assess, in PCOS women, the relationship between ALT levels and measures of lipotoxicity consequences that are available clinically, both during fasting and using the oral glucose tolerance test...
April 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28335507/hydroxytyrosol-in-the-prevention-of-the-metabolic-syndrome-and-related-disorders
#4
REVIEW
Julien Peyrol, Catherine Riva, Marie Josèphe Amiot
Virgin olive oil (VOO) constitutes the main source of fat in the Mediterranean diet. VOO is rich in oleic acid, displaying health-promoting properties, but also contains minor bioactive components, especially phenolic compounds. Hydroxytyrosol (HT), the main polyphenol of olive oil, has been reported to be the most bioactive component. This review aims to compile the results of clinical, animal and cell culture studies evaluating the effects of HT on the features of Metabolic Syndrome (MetS) (body weight/adiposity, dyslipidemia, hypertension, and hyperglycemia/insulin resistance) and associated complications (oxidative stress and inflammation)...
March 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28334911/mertk-rs4374383-variant-predicts-incident-nonalcoholic-fatty-liver-disease-and-diabetes-role-of-mononuclear-cell-activation-and-adipokine-response-to-dietary-fat
#5
Giovanni Musso, Maurizio Cassader, Franco De Michieli, Elena Paschetta, Silvia Pinach, Francesca Saba, Daria Bongiovanni, Luciana Framarin, Mara Berrutti, Nicola Leone, Stefania Corvisieri, Renato Parente, Federica Molinaro, Antonio Sircana, Bo Simona, Roberto Gambino
The loss-of-function rs4374383 G>A variant in Myeloid-epithelial-reproductive Tyrosine Kinase (MERTK) gene has been linked to hepatic fibrosis in chronic liver diseases. MERTK is expressed by immune and non-immune cells involved in inflammation, metabolism and vascular homeostasis. We assessed the impact of MERTK rs4374383 G>A variant on nonalcoholic fatty liver disease (NAFLD) incidence and severity and on glucose and lipid metabolism.We followed-up 305 healthy nonobese nondiabetic, metabolic syndrome-free insulin sensitive participants in a population-based study, characterized for MERTK G>A polymorphism, adipokine profile and inflammatory markers...
March 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334807/allele-specific-quantitative-proteomics-unravels-molecular-mechanisms-modulated-by-cis-regulatory-pparg-locus-variation
#6
Heekyoung Lee, Kun Qian, Christine von Toerne, Lena Hoerburger, Melina Claussnitzer, Christoph Hoffmann, Viktoria Glunk, Simone Wahl, Michaela Breier, Franziska Eck, Leili Jafari, Sophie Molnos, Harald Grallert, Ingrid Dahlman, Peter Arner, Cornelia Brunner, Hans Hauner, Stefanie M Hauck, Helmut Laumen
Genome-wide association studies identified numerous disease risk loci. Delineating molecular mechanisms influenced by cis-regulatory variants is essential to understand gene regulation and ultimately disease pathophysiology. Combining bioinformatics and public domain chromatin information with quantitative proteomics supports prediction of cis-regulatory variants and enabled identification of allele-dependent binding of both, transcription factors and coregulators at the type 2 diabetes associated PPARG locus...
February 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334683/combined-metformin-and-insulin-treatment-reverses-metabolically-impaired-omental-adipogenesis-and-accumulation-of-4-hydroxynonenal-in-obese-diabetic-patients
#7
Morana Jaganjac, Shamma Almuraikhy, Fatima Al-Khelaifi, Mashael Al-Jaber, Moataz Bashah, Nayef A Mazloum, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Wael Kafienah, Mohamed A Elrayess
OBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery...
March 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28333384/transcriptional-regulation-of-adipogenesis
#8
Paula Mota de Sá, Allison J Richard, Hardy Hang, Jacqueline M Stephens
Adipocytes are the defining cell type of adipose tissue. Once considered a passive participant in energy storage, adipose tissue is now recognized as a dynamic organ that contributes to several important physiological processes, such as lipid metabolism, systemic energy homeostasis, and whole-body insulin sensitivity. Therefore, understanding the mechanisms involved in its development and function is of great importance. Adipocyte differentiation is a highly orchestrated process which can vary between different fat depots as well as between the sexes...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333286/high-prevalence-of-moderate-and-severe-depressive-and-anxiety-symptoms-in-polycystic-ovary-syndrome-a-systematic-review-and-meta-analysis
#9
Laura G Cooney, Iris Lee, Mary D Sammel, Anuja Dokras
Study question: Do women with polycystic ovary syndrome (PCOS) have an increased prevalence of moderate and severe depressive and anxiety symptoms compared with control women, and do these symptoms correlate with age, BMI, testosterone, hirsutism or insulin resistance (IR)? Summary answer: Women with PCOS have significantly increased odds of moderate and severe depressive and anxiety symptoms, independent of obesity, and the symptoms are weakly associated with age, BMI, elevated testosterone, hirsutism and IR...
March 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28333091/marine-peptides-as-potential-agents-for-the-management-of-type-2-diabetes-mellitus-a-prospect
#10
REVIEW
En-Qin Xia, Shan-Shan Zhu, Min-Jing He, Fei Luo, Cheng-Zhan Fu, Tang-Bin Zou
An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans. We summarized here recent advances in our understanding of the regulation of glucose metabolism using bioactive peptides from natural proteins, including regulation of insulin-regulated glucose metabolism, such as protection and reparation of pancreatic β-cells, enhancing glucose-stimulated insulin secretion and influencing the sensitivity of insulin and the signaling pathways, and inhibition of bioactive peptides to dipeptidyl peptidase IV, α-amylase and α-glucosidase activities...
March 23, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28332074/matrix-metalloproteinase-2-mmp-2-levels-are-increased-in-active-acromegaly-patients
#11
Alper Cagri Karci, Zeynep Canturk, Ilhan Tarkun, Berrin Cetinarslan
PURPOSE: During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. METHODS: In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40)...
March 22, 2017: Endocrine
https://www.readbyqxmd.com/read/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#12
Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee
AIMS: Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. METHODS: Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included...
March 22, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28331909/evaluating-the-effect-of-insulin-sensitizers-metformin-and-pioglitazone-alone-and-in-combination-on-women-with-polycystic-ovary-syndrome-an-rct
#13
Seyed Mojtaba Sohrevardi, Fahime Nosouhi, Saeed Hossein Khalilzade, Parichehr Kafaie, Mojgan Karimi-Zarchi, Iman Halvaei, Mehdi Mohsenzadeh
BACKGROUND: Insulin resistance and hyperinsulinemia may play a role in pathogenesis of PCOS. One of the common therapeutic methods is using insulin-sensitizing drugs such as metformin and thiazolidinediones. OBJECTIVE: The purpose was to determine the effect of metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. MATERIALS AND METHODS: Eighty four women randomly received one of the following for 3 months: metformin (n=28) (500 mg three times a day), pioglitazone (30 mg daily) (n=28) and combination of both metformin and pioglitazone (n=28) (30 mg/day pioglitazone plus 500 mg metformin three times a day)...
December 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/28330882/adiponectin-and-resistin-a-role-in-the-hypothalamo-pituitary-gonadal-axis
#14
Agnieszka Rak, Namya Mellouk, Pascal Froment, Joëlle Dupont
Adipokines, including adiponectin and resistin, are cytokines produced mainly by adipose tissue. They play a significant role in the metabolic functions that regulate insulin sensitivity and inflammation. Alteration of adiponectin and resistin plasma levels, or their expression in metabolic and gonadal tissue, are observed in some metabolic pathologies, such as obesity. Several studies have shown that these two hormones and the receptors for adiponectin, AdipoR1 and AdipoR2, are present in various reproductive tissues in both sexes of different species...
March 22, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28330649/effect-of-sacubitril-valsartan-versus-enalapril-on-glycaemic-control-in-patients-with-heart-failure-and-diabetes-a-post-hoc-analysis-from-the-paradigm-hf-trial
#15
Jelena P Seferovic, Brian Claggett, Sara B Seidelmann, Ellen W Seely, Milton Packer, Michael R Zile, Jean L Rouleau, Karl Swedberg, Martin Lefkowitz, Victor C Shi, Akshay S Desai, John J V McMurray, Scott D Solomon
BACKGROUND: Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF...
March 17, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28329950/-progress-in-research-of-association-between-sleep-duration-and-type-2-diabetes
#16
H B Wu, L Yang, M Yu, J M Zhong, R Y Hu
Diabetes has become the world' s major public health problem in the 21(th) century. Increasing attention has been paid to the importance of healthy sleep abroad, whereas less attention has been paid to it in China. Through literature study, this paper summarizes the current status of epidemiology and laboratory research on the relationship between sleep duration and incidence of type 2 diabetes, insulin sensitivity and blood glucose control both at home and abroad, and introduces the underlying mechanisms in order to provide evidence for further studies and the prevention and management of diabetes...
March 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28329397/resveratrol-improves-vascular-function-and-mitochondrial-number-but-not-glucose-metabolism-in-older-adults
#17
Rena M Pollack, Nir Barzilai, Valentin Anghel, Ameya S Kulkarni, Aaron Golden, Pilib O'Broin, David A Sinclair, Michael S Bonkowski, Alexander J Coleville, Danielle Powell, Sharon Kim, Ruin Moaddel, Daniel Stein, Kehao Zhang, Meredith Hawkins, Jill P Crandall
Background: Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive. Methods: In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry...
March 16, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28329361/sex-hormones-affect-outcome-in-arrhythmogenic-right-ventricular-cardiomyopathy-dysplasia-from-a-stem-cell-derived-cardiomyocyte-based-model-to-clinical-biomarkers-of-disease-outcome
#18
Deniz Akdis, Ardan M Saguner, Khooshbu Shah, Chuanyu Wei, Argelia Medeiros-Domingo, Arnold von Eckardstein, Thomas F Lüscher, Corinna Brunckhorst, H S Vincent Chen, Firat Duru
Aims: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. Methods and results: The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male)...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28329008/insulin-and-diet-induced-changes-in-the-ubiquitin-modified-proteome-of-rat-liver
#19
Shilpa R Nagarajan, Amanda E Brandon, Jessie A McKenna, Harrison C Shtein, Thinh Q Nguyen, Eurwin Suryana, Philip Poronnik, Gregory J Cooney, Darren N Saunders, Andrew J Hoy
Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28328533/plasma-but-not-serum-brain-derived-neurotrophic-factor-concentration-is-decreased-by-oral-glucose-tolerance-test-induced-hyperglycemia-in-children
#20
Shunsuke Araki, Yukiyo Yamamoto, Reiko Saito, Aoi Kawakita, Mami Eguchi, Motohide Goto, Kazuyasu Kubo, Rinko Kawagoe, Yasusada Kawada, Koichi Kusuhara
BACKGROUND: Little is known regarding the relationships among circulating brain-derived neurotrophic factor (BDNF) levels and glucose or insulin in children and adolescents. The objective of this study was to investigate whether circulating BDNF levels would change during the oral glucose tolerance test (OGTT). METHODS: We performed the OGTT and measured the serial changes in BDNF levels in both plasma and serum. RESULTS: There were 22 subjects in the normal type (N) group and 20 in the borderline/diabetic type (B/D) group, defined by the results of the OGTT...
March 22, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
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