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Succinate diabetes

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https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#1
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, 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 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 epi-metabolic 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 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: 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
#2
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
#3
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
#4
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
#5
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%)...
October 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29070571/lithium-induces-aerobic-glycolysis-and-glutaminolysis-in-collecting-duct-principal-cells
#6
Mohammad Alsady, Theun de Groot, Marleen Louise Adriënne 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 is 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. Earlier, we have shown 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...
October 25, 2017: 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
#7
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
https://www.readbyqxmd.com/read/29026604/transglucosidase-improves-the-bowel-movements-in-type-2-diabetes-mellitus-patients-a-preliminary-randomized-double-blind-placebo-controlled-study
#8
Akihiro Shimozato, Makoto Sasaki, Naotaka Ogasawara, Yasushi Funaki, Masahide Ebi, Chiho Goto, Satoshi Koikeda, Takashi Joh, Kunio Kasugai
BACKGROUND: Recent studies have highlighted the relationship between gut microbiota and bowel movements. OBJECTIVE: We aimed to evaluate transglucosidase treatment efficacy for bowel movements in patients with type 2 diabetes mellitus and to clarify the relationship between bowel movements, dietary habits, gut microbiota and fecal short-chain fatty acids. METHODS: In this randomized double-blind, placebo-controlled study, 66 patients received placebo or transglucosidase (300 or 900 mg/day) orally, for 12 weeks...
October 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28954230/fumarate-hydratase-deletion-in-pancreatic-%C3%AE-cells-leads-to-progressive-diabetes
#9
Julie Adam, Reshma Ramracheya, Margarita V Chibalina, Nicola Ternette, Alexander Hamilton, Andrei I Tarasov, Quan Zhang, Eduardo Rebelato, Nils J G Rorsman, Rafael Martín-Del-Río, Amy Lewis, Gizem Özkan, Hyun Woong Do, Peter Spégel, Kaori Saitoh, Keiko Kato, Kaori Igarashi, Benedikt M Kessler, Christopher W Pugh, Jorge Tamarit-Rodriguez, Hindrik Mulder, Anne Clark, Norma Frizzell, Tomoyoshi Soga, Frances M Ashcroft, Andrew Silver, Patrick J Pollard, Patrik Rorsman
We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca(2+)]i elevation, and GSIS...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28874953/pleiotropic-effects-of-biguanides-on-mitochondrial-reactive-oxygen-species-production
#10
Alena Pecinova, Zdenek Drahota, Jana Kovalcikova, Nikola Kovarova, Petr Pecina, Lukas Alan, Michal Zima, Josef Houstek, Tomas Mracek
Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28815303/effect-of-barley-supplementation-on-the-fecal-microbiota-caecal-biochemistry-and-key-biomarkers-of-obesity-and-inflammation-in-obese-db-db-mice
#11
Jose F Garcia-Mazcorro, David A Mills, Kevin Murphy, Giuliana Noratto
PURPOSE: Barley is a low-glycemic index grain that can help diabetic and obese patients. The effect of barley intake depends on the host and the associated gut microbiota. This study investigated the effect of barley intake on the fecal microbiota, caecal biochemistry, and key biomarkers of obesity and inflammation. METHODS: Obese db/db mice were fed diets with and without barley during 8 weeks; lean mice were used as lean controls. Fecal microbiota was evaluated using 16S marker gene sequencing in a MiSeq instrument; several markers of caecal biochemistry, obesity, and inflammation were also evaluated using standard techniques...
August 16, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28814103/annals-express-associations-between-glycaemic-control-and-activation-of-the-renin-angiotensin-aldosterone-system-in-participants-with-type-2-diabetes-mellitus-and-hypertension
#12
Tomas Patrick Griffin, Deirdre Wall, Gerard A Browne, Michael C Dennedy, Paula O'Shea
INTRODUCTION: Hyperglycaemia increases succinate levels and succinate receptor (GPR91) activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin (HbA1c) values and activation of the renin-angiotensin-aldosterone-system in patients with type 2 diabetes mellitus (T2DM) and hypertension. METHODS: A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28813209/galangin-a-natural-flavonoid-reduces-mitochondrial-oxidative-damage-in-streptozotocin-induced-diabetic-rats
#13
Amal A Aloud, Chinnadurai Veeramani, Chandramohan Govindasamy, Mohammed A Alsaif, Khalid S Al-Numair
OBJECTIVE: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats. METHODS: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40 mg kg(-1) body weight (BW)). Galangin (8 mg kg(-1) BW) or glibenclamide (600 µg kg(-1) BW) was given orally daily once for 45 days to both healthy and diabetic rats. RESULTS: Diabetic rats showed significant (P < 0...
August 16, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28780379/proinflammatory-cytokine-mif-plays-a-role-in-the-pathogenesis-of-type-2-diabetes-mellitus-but-does-not-affect-hepatic-mitochondrial-function
#14
Miriam Rodriguez-Sosa, Tecilli Cabellos-Avelar, Yuriko Sanchez-Zamora, Imelda Juárez-Avelar, Esperanza García-Reyes, Alejandra Lira-León, José Del Carmen Benítez-Flores, Thalia Pacheco-Fernández, Marcia Hiriart, Emma Berta Gutiérrez-Cirlos
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Although the effect of high glucose on liver function has been described, the role of MIF in hepatic mitochondrial function during T2DM has not been studied. OBJECTIVE: We examine the influence of MIF to hepatic mitochondrial function in T2DM mouse model. METHODS: WT and Mif(-/-) BALB/c mice were treated with a single dose of streptozotocin (STZ)...
August 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28763556/modifications-in-retinal-mitochondrial-respiration-precede-type-2-diabetes-and-protracted-microvascular-retinopathy
#15
Woo Hyun Han, Jonathan Gotzmann, Sharee Kuny, Hui Huang, Catherine B Chan, Hélène Lemieux, Yves Sauvé
Purpose: To characterize retinal mitochondrial respiration associated with type 2 diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus Arvicanthis, species niloticus). Methods: Nile rats were fed a standard rodent diet that resulted in rising glucose levels from 6 months. Age-matched control animals were fed a high-fiber diet that prevented diabetes up to 18 months. The functional status of specific retinal mitochondrial components and mitochondrial outer membrane integrity were studied by using high-resolution respirometry...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28738167/methylene-blue-improves-mitochondrial-respiration-and-decreases-oxidative-stress-in-a-substrate-dependent-manner-in-diabetic-rat-hearts
#16
Oana M Duicu, Andreea Privistirescu, Adrian Wolf, Alexandra Petruş, Maria D Dănilă, Corina D Raţiu, Danina M Muntean, Adrian Sturza
Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H2O2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats...
November 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28638031/-anxiolytic-and-antidepressant-effects-of-emoxipine-reamberin-and-mexidol-in-experimental-diabetes-mellitus
#17
I A Volchegorskii, I Yu Miroshnichenko, L M Rassokhina, R M Faizullin, K E Pryakhina
AIM: To perform a comparative study of anxiolytic and antidepressant effects of derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin and mexidol) in experimental diabetes mellitus. MATERIAL AND METHODS: An effect of emoxipine, reamberin and mexidol on manifestations of anxiety in 'elevated plus maze' (EPM) and duration of 'desperate behavior' (DB) in Porsolt test in rats with alloxan diabetes during medication course was studied. Alpha-lipoic (thioctic) acid (α-LA) was used as a reference drug...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28626178/hypoglycemic-coma-induced-by-the-use-of-succinic-acid-cibenzoline-in-frail-late-stage-elderly-subjects
#18
Yurie Hirata, Shinji Kamei, Fuminori Tatsumi, Masashi Shimoda, Akihito Tanabe, Junpei Sanada, Yoshiro Fushimi, Shintaro Irie, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
Succinic acid cibenzoline (CZ) is an antiarrhythmic agent often used for the treatment of tachyarrhythmia. However, hypoglycemia should be avoided in the treatment of diabetes. We herein report two late-stage elderly subjects who experienced a severe and prolonged hypoglycemic coma after the usage of CZ. These cases suggest that, when CZ is administered to elderly subjects with renal dysfunction and/or frailty, we should be aware of the possibility that this medicine may induce hypoglycemia and should adjust the dose as appropriate and monitor the concentration of CZ to avoid severe hypoglycemia...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28617536/effects-of-mulberry-leaf-polysaccharide-on-oxidative-stress-in-pancreatic-%C3%AE-cells-of-type-2-diabetic-rats
#19
C-G Liu, Y-P Ma, X-J Zhang
OBJECTIVE: To explore and discuss the effects and mechanisms of mulberry leaf polysaccharide (MLP) on oxidative stress in pancreatic β-cells of type 2 diabetic rats. MATERIALS AND METHODS: The model of diabetic rats was established by inducing the Sprague-Dawley (SD) rats with high-sugar and high-fat diet for 6 weeks and then giving them streptozotocin (STZ) by single intraperitoneal injection. The mulberry leaf polysaccharide was administered via gavage daily for 8 weeks, and the tissue morphology was observed through electron microscopy...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28593900/phellinus-rimosus-improves-mitochondrial-energy-status-and-attenuates-nephrotoxicity-in-diabetic-rats
#20
K A Rony, T A Ajith, Tony A Kuttikadan, R Blaze, K K Janardhanan
BACKGROUND: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. METHODS: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation...
September 26, 2017: Journal of Basic and Clinical Physiology and Pharmacology
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