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Succinate diabetes

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https://www.readbyqxmd.com/read/29772565/safety-of-iohexol-administration-to-measure-glomerular-filtration-rate-in-different-patient-populations-a-25-year-experience
#1
Flavio Gaspari, Surabhi Thakar, Fabiola Carrara, Annalisa Perna, Matias Trillini, Maria Carolina Aparicio, Olimpia Diadei, Silvia Ferrari, Antonio Cannata, Nadia Stucchi, Piero Ruggenenti, Giuseppe Remuzzi, Norberto Perico
BACKGROUND/AIM: In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR) is essential to overcome the limitations of GFR estimation with equations, which are often unreliable. In recent decades, a method for measuring GFR by plasma clearance of iohexol, a non-ionic radiocontrast agent, was developed. To evaluate the safety of the procedure, we aimed to review all immediate adverse reactions that could be related to iohexol administration in our group's 25 years worth of experience...
May 17, 2018: Nephron
https://www.readbyqxmd.com/read/29754646/effect-of-carvedilol-vs-metoprolol-succinate-on-mortality-in-heart-failure-with-reduced-ejection-fraction
#2
Tarek Ajam, Samer Ajam, Srikant Devaraj, Kahee Mohammed, Stephen Sawada, Masoor Kamalesh
BACKGROUND: Beta blocker therapy is indicated in all patients with heart failure with reduced ejection fraction (HFrEF) as per current guidelines. The relative benefit of carvedilol to metoprolol succinate remains unknown. This study aimed to compare survival benefit of carvedilol to metoprolol succinate. METHODS: The VA's databases were queried to identify 114,745 patients diagnosed with HFrEF from 2007 to 2015 who were prescribed carvedilol and metoprolol succinate...
May 2018: American Heart Journal
https://www.readbyqxmd.com/read/29742293/glycemic-status-affects-the-subgingival-microbiome-of-diabetic-patients
#3
Priscila Larcher Longo, Shareef Dabdoub, Purnima Kumar, Hilana Paula Carillo Artese, Sergio Atala Dib, Giuseppe Alexandre Romito, Marcia Pinto Alves Mayer
AIM: Periodontitis is correlated with type 2 diabetes mellitus (T2DM), but little is known about glycemic status effect on subgingival microbiota associated with periodontitis. This study evaluated if periodontal microbiome of T2DM patients is affected by glycemic status. MATERIALS AND METHODS: 21 T2DM non-smoking patients with chronic periodontitis and body mass index ≤40kg/m2 were allocated into two groups according to systemic glycemic status: inadequate (DMI- HbA1c≥8%) and adequate (DMA- HbA1c<7...
May 9, 2018: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/29686903/streptozotocin-induced-adaptive-modification-of-mitochondrial-supercomplexes-in-liver-of-wistar-rats-and-the-protective-effect-of-moringa-oleifera-lam
#4
María Alejandra Sánchez-Muñoz, Mónica Andrea Valdez-Solana, Mara Ibeth Campos-Almazán, Óscar Flores-Herrera, Mercedes Esparza-Perusquía, Sofia Olvera-Sánchez, Guadalupe García-Arenas, Claudia Avitia-Domínguez, Alfredo Téllez-Valencia, Erick Sierra-Campos
The increasing prevalence of diabetes continues to be a major health issue worldwide. Alteration of mitochondrial electron transport chain is a recognized hallmark of the diabetic-associated decline in liver bioenergetics; however, the molecular events involved are only poorly understood. Moringa oleifera is used for the treatment of diabetes. However, its role on mitochondrial functionality is not yet established. This study was aimed to evaluate the effect of M. oleifera extract on supercomplex formation, ATPase activity, ROS production, GSH levels, lipid peroxidation, and protein carbonylation...
2018: Biochemistry Research International
https://www.readbyqxmd.com/read/29626092/identification-of-a-metabolic-disposal-route-for-the-oncometabolite-s-2-succino-cysteine-in-bacillus-subtilis
#5
Thomas D Niehaus, Jacob Folz, Donald R McCarty, Arthur J L Cooper, David Moraga Amador, Oliver Fiehn, Andrew D Hanson
Cellular thiols such as cysteine spontaneously and readily react with the respiratory intermediate fumarate, resulting in the formation of stable S -(2-succino)-adducts. Fumarate-mediated succination of thiols increases in certain tumors and in response to glucotoxicity associated with diabetes. Therefore, S -(2-succino)-adducts such as S -(2-succino)cysteine (2SC) are considered oncometabolites and biomarkers for human disease. No disposal routes for S -(2-succino) compounds have been reported prior to this study...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29614759/high-glucose-induced-cardiomyocyte-death-may-be-linked-to-unbalanced-branched-chain-amino-acids-and-energy-metabolism
#6
Xi Zhang, Qiuting Lin, Jiuxia Chen, Tingting Wei, Chen Li, Liangcai Zhao, Hongchang Gao, Hong Zheng
High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo...
April 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29507942/effect-of-treating-acute-optic-neuritis-with-bioequivalent-oral-vs-intravenous-corticosteroids-a-randomized-clinical-trial
#7
Sarah A Morrow, J Alexander Fraser, Chad Day, Denise Bowman, Heather Rosehart, Marcelo Kremenchutzky, Michael Nicolle
Importance: Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis. Objective: To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid...
March 5, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29445185/iron-overload-accelerates-the-progression-of-diabetic-retinopathy-in-association-with-increased-retinal-renin-expression
#8
Kapil Chaudhary, Wanwisa Promsote, Sudha Ananth, Rajalakshmi Veeranan-Karmegam, Amany Tawfik, Pachiappan Arjunan, Pamela Martin, Sylvia B Smith, Muthusamy Thangaraju, Oleg Kisselev, Vadivel Ganapathy, Jaya P Gnana-Prakasam
Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29434314/elevated-circulating-levels-of-succinate-in-human-obesity-are-linked-to-specific-gut-microbiota
#9
Carolina Serena, Victoria Ceperuelo-Mallafré, Noelia Keiran, Maria Isabel Queipo-Ortuño, Rosa Bernal, Ricardo Gomez-Huelgas, Mireia Urpi-Sarda, Mónica Sabater, Vicente Pérez-Brocal, Cristina Andrés-Lacueva, Andres Moya, Francisco J Tinahones, Jose Manuel Fernández-Real, Joan Vendrell, Sonia Fernández-Veledo
Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects...
February 12, 2018: ISME Journal
https://www.readbyqxmd.com/read/29278707/metformin-ameliorates-activation-of-hepatic-stellate-cells-and-hepatic-fibrosis-by-succinate-and-gpr91-inhibition
#10
Giang Nguyen, So Young Park, Cong Thuc Le, Won Sun Park, Dae Hee Choi, Eun-Hee Cho
BACKGROUND: Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA)...
January 22, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29204172/protective-effects-of-coenzyme-q-10-and-l-carnitine-against-statin-induced-pancreatic-mitochondrial-toxicity-in-rats
#11
Melina Sadighara, Jalal Pourahamad Joktaji, Valiollah Hajhashemi, Mohsen Minaiyan
Statins are widely used in patients with hyperlipidemia and whom with high risk of cardiovascular diseases. Unfortunately, statins also exert some adverse effects on the liver and pancreas and enhance the risk of type 2 diabetes mellitus. The objective of the present research was to investigate the protective effects of coenzyme Q10 (Co-Q10 ) and L-carnitine (LC) on statins induced toxicity on pancreatic mitochondria in vivo . Seven groups of male Wistar rats received atorvastatin (20 mg/kg, p.o.), atorvastatin + Co-Q10 (10 mg/kg, i...
December 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29197503/serum-metabolic-profiling-of-type-2-diabetes-mellitus-in-chinese-adults-using-an-untargeted-gc-tofms
#12
Huijuan Wang, Hailong Zhang, Ling Yao, Longzhen Cui, Lei Zhang, Biao Gao, Wen Liu, Dongdong Wu, Mingliang Chen, Xue Li, Ailing Ji, Yanzhang Li
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a huge burden in China. The Chinese patients with T2DM have several special clinical characteristics. Metabolomics studies predominantly have identified several distinguishing metabolites associated with T2DM in Western ancestry population. However, few previous metabolomics studies were conducted in Chinese populations. METHODS: We performed untargeted serum metabolic profiling between 30 T2DM patients and 30 healthy controls based on GC/TOFMS...
February 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29182580/genes-and-gut-bacteria-involved-in-luminal-butyrate-reduction-caused-by-diet-and-loperamide
#13
Nakwon Hwang, Taekil Eom, Sachin K Gupta, Seong-Yeop Jeong, Do-Youn Jeong, Yong Sung Kim, Ji-Hoon Lee, Michael J Sadowsky, Tatsuya Unno
Unbalanced dietary habits and gut dysmotility are causative factors in metabolic and functional gut disorders, including obesity, diabetes, and constipation. Reduction in luminal butyrate synthesis is known to be associated with gut dysbioses, and studies have suggested that restoring butyrate formation in the colon may improve gut health. In contrast, shifts in different types of gut microbiota may inhibit luminal butyrate synthesis, requiring different treatments to restore colonic bacterial butyrate synthesis...
November 28, 2017: Genes
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-%C3%AE-ketoglutarate-and-tet-tdg-functional-reactivation
#14
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Kuenne, Stefan Guenther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sürün, Frank Schnütgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
RATIONALE: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. OBJECTIVE: To investigate the role of α-ketoglutarate (αKG) in the epimetabolic control of DNA demethylation in CMSCs. METHODS AND RESULTS: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing, and gene-specific GC methylation detection revealed an accumulation of 5-methylcytosine, 5-hydroxymethylcytosine, and 5-formylcytosine in the genomic DNA of human CMSCs isolated from diabetic donors...
January 5, 2018: Circulation Research
https://www.readbyqxmd.com/read/29157816/effect-of-ipomoea-aquatica-ethanolic-extract-in-streptozotocin-stz-induced-diabetic-rats-via-1-h-nmr-based-metabolomics-approach
#15
Azliana Abu Bakar Sajak, Ahmed Mediani, Maulidiani, Nur Sumirah Mohd Dom, Chandradevan Machap, Muhajir Hamid, Amin Ismail, Alfi Khatib, Faridah Abas
BACKGROUND: Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown. PURPOSE: This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157600/receptor-structure-based-discovery-of-non-metabolite-agonists-for-the-succinate-receptor-gpr91
#16
Mette Trauelsen, Elisabeth Rexen Ulven, Siv A Hjorth, Matjaz Brvar, Claudia Monaco, Thomas M Frimurer, Thue W Schwartz
OBJECTIVE: Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS: Here we first determined that the cis conformation of the succinate backbone is preferred and that certain backbone modifications are allowed for GPR91 activation. Through receptor modeling over the X-ray structure of the closely related P2Y1 receptor, we discovered that the binding pocket is partly occupied by a segment of an extracellular loop and that succinate therefore binds in a very different mode than generally believed...
December 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29137485/heat-stress-prevents-the-decrease-in-succinate-dehydrogenase-activity-in-the-extensor-digitorum-longus-of-streptozotocin-induced-diabetic-rats
#17
K Nonaka, S Une, M Komatsu, R Yamaji, J Akiyama
This study aimed to investigate whether heat stress (HS) prevents a decrease in succinate dehydrogenase (SDH) activity and heat shock protein 60 (HSP60) and superoxide dismutase 2 (SOD2) contents in the extensor digitorum longus of streptozotocin (STZ)-induced diabetic rats. Twelve-week-old male Wistar rats were assigned to one of the four groups (n=6/group): control (Con), HS, diabetes mellitus (DM), and diabetes mellitus and heat stress (DM+HS). Diabetes was induced by the administration of STZ (50 mg/kg)...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29128444/metabolomics-and-gene-expression-analysis-reveal-down-regulation-of-the-citric-acid-tca-cycle-in-non-diabetic-ckd-patients
#18
Stein Hallan, Maryam Afkarian, Leila R Zelnick, Bryan Kestenbaum, Shoba Sharma, Rintaro Saito, Manjula Darshi, Gregory Barding, Daniel Raftery, Wenjun Ju, Matthias Kretzler, Kumar Sharma, Ian H de Boer
Chronic kidney disease (CKD) is a public health problem with very high prevalence and mortality. Yet, there is a paucity of effective treatment options, partly due to insufficient knowledge of underlying pathophysiology. We combined metabolomics (GCMS) with kidney gene expression studies to identify metabolic pathways that are altered in adults with non-diabetic stage 3-4 CKD versus healthy adults. Urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed significantly in CKD patients versus controls (estimate range-68% to +113%)...
December 2017: EBioMedicine
https://www.readbyqxmd.com/read/29070571/lithium-induces-aerobic-glycolysis-and-glutaminolysis-in-collecting-duct-principal-cells
#19
Mohammad Alsady, Theun de Groot, Marleen L A Kortenoeven, Claudia Carmone, Kim Neijman, Melissa Bekkenkamp-Grovenstein, Udo Engelke, Ron Wevers, Ruben Baumgarten, Ron Korstanje, Peter M T Deen
Lithium, given to bipolar disorder patients, causes nephrogenic diabetes insipidus (Li-NDI), a urinary-concentrating defect. Li-NDI occurs due to downregulation of principal cell AQP2 expression, which coincides with principal cell proliferation. The metabolic effect of lithium on principal cells, however, is unknown and investigated here. In earlier studies, we showed that the carbonic anhydrase (CA) inhibitor acetazolamide attenuated Li-induced downregulation in mouse-collecting duct (mpkCCD) cells. Of the eight CAs present in mpkCCD cells, siRNA and drug treatments showed that downregulation of CA9 and to some extent CA12 attenuated Li-induced AQP2 downregulation...
February 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29066384/development-of-a-validated-hplc-method-for-the-quantitative-determination-of-trelagliptin-succinate-and-its-related-substances-in-pharmaceutical-dosage-forms
#20
Zhiqiang Luo, Xinjing Chen, Guopeng Wang, Zhibo Du, Xiaoyun Ma, Hao Wang, Guohua Yu, Aoxue Liu, Mengwei Li, Wei Peng, Yang Liu
Trelagliptin succinate is a dipeptidyl peptidase IV (DPP-4) inhibitor which is used as a new long-acting drug for once-weekly treatment of type 2 diabetes mellitus (DM). In the present study, a rapid, sensitive and accurate high-performance liquid chromatography (HPLC) method was developed and validated for separation and determination of trelagliptin succinate and its eight potential process-related impurities. The chromatographic separation was achieved on a Waters Xselect CSH™ C18 (250mm×4.6mm, 5.0μm) column...
October 21, 2017: European Journal of Pharmaceutical Sciences
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