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NADH AND diabetes

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https://www.readbyqxmd.com/read/28887630/ncb5or-deficiency-in-the-cerebellum-and-midbrain-leads-to-dehydration-and-alterations-in-thirst-response-fasted-feeding-behavior-and-voluntary-exercise-in-mice
#1
Matthew A Stroh, Michelle K Winter, Kenneth E McCarson, John P Thyfault, Hao Zhu
Cytosolic NADH-cytochrome-b5-oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues. We have previously reported that global ablation of NCB5OR in mice results in early-onset lean diabetes with decreased serum leptin levels and increased metabolic and feeding activities. The conditional deletion of NCB5OR in the mouse cerebellum and midbrain (conditional knock out, CKO mice) results in local iron dyshomeostasis and altered locomotor activity. It has been established that lesion to or removal of the cerebellum leads to changes in nutrient organization, visceral response, feeding behavior, and body weight...
September 8, 2017: Cerebellum
https://www.readbyqxmd.com/read/28875237/uncoupling-protein-2-inhibition-exacerbates-glucose-fluctuation-mediated-neuronal-effects
#2
Susana Cardoso, Raquel M Seiça, Paula I Moreira
Though glucose fluctuations have been considered as an adverse factor for the development of several diabetes-related complications, their impact in the central nervous system is still not fully elucidated. This study was conducted to evaluate the responses of neuronal cells to different glycemic exposures alongside to elucidate the role of uncoupling protein 2 (UCP2) in regulating such responses. To achieve our goals, primary cortical neurons were submitted to constant high (HG)/low (LG) or glucose level variations (GVs), and the pharmacological inhibition of UCP2 activity was performed using genipin...
September 5, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28874953/pleiotropic-effects-of-biguanides-on-mitochondrial-reactive-oxygen-species-production
#3
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/28868496/pancreatic-mitochondrial-complex-i-exhibits-aberrant-hyperactivity-in-diabetes
#4
Jinzi Wu, Xiaoting Luo, Nopporn Thangthaeng, Nathalie Sumien, Zhenglan Chen, Margaret A Rutledge, Siqun Jing, Michael J Forster, Liang-Jun Yan
It is well established that NADH/NAD(+) redox balance is heavily perturbed in diabetes, and the NADH/NAD(+) redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD(+) regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD(+) redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28840593/a-pilot-study-with-flow-mediated-skin-fluorescence-a-novel-device-to-assess-microvascular-endothelial-function-in-coronary-artery-disease
#5
Maria Tarnawska, Karolina Dorniak, Mariusz Kaszubowski, Maria Dudziak, Marcin Hellmann
BACKGROUND: Endothelial dysfunction is one of the earliest vascular manifestations in the pathogenesis of cardiovascular disease. Noninvasive, simple and inexpensive methods of endothelial function assessment are therefore needed. METHODS: Microvascular endothelial function was assessed in coronary artery disease (CAD) patients by flow mediated skin fluorescence (FMSF), based on measurements of NADH fluorescence intensity during brachial artery occlusion (ischemic response [IRmax]) and immediately after occlusion (hyperemic response [HRmax])...
August 25, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28813209/galangin-a-natural-flavonoid-reduces-mitochondrial-oxidative-damage-in-streptozotocin-induced-diabetic-rats
#6
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/28763556/modifications-in-retinal-mitochondrial-respiration-precede-type-2-diabetes-and-protracted-microvascular-retinopathy
#7
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/28754553/real-time-in%C3%A2-vivo-mitochondrial-redox-assessment-confirms-enhanced-mitochondrial-reactive-oxygen-species-in-diabetic-nephropathy
#8
Daniel L Galvan, Shawn S Badal, Jianyin Long, Benny H Chang, Paul T Schumacker, Paul A Overbeek, Farhad R Danesh
While increased mitochondrial reactive oxygen species have been commonly implicated in a variety of disease states, their in vivo role in the pathogenesis of diabetic nephropathy remains controversial. Using a two-photon imaging approach with a genetically encoded redox biosensor, we monitored mitochondrial redox state in the kidneys of experimental models of diabetes in real-time in vivo. Diabetic (db/db) mice that express a redox-sensitive Green Fluorescent Protein biosensor (roGFP) specifically in the mitochondrial matrix (db/dbmt-roGFP) were generated, allowing dynamic monitoring of redox changes in the kidneys...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28701960/role-of-mitochondrial-reverse-electron-transport-in-ros-signaling-potential-roles-in-health-and-disease
#9
REVIEW
Filippo Scialò, Daniel J Fernández-Ayala, Alberto Sanz
Reactive Oxygen Species (ROS) can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28598104/-association-of-nt3434a-8594-g-mutation-in-mitochondrial-dna-nd1-gene-with-diabetes-mellitus
#10
Xi Wang, Yan Ren, Wen Wang, Jie Song, Yang Long, Hao-Ming Tian, Hong-Ling Yu, Xiang-Xun Zhang
OBJECTIVES: To study the association of nt3434 A→G mutation in mitochondrial DNA NADH dehydrogenase 1 subunit (ND1) gene with diabetes mellitus. METHODS: PCR-RFLP was used to detect the nt3434 A→G variant of mtDNA ND1 gene in 216 diabetic patients and 203 healthy control individuals. Characteristics of mutation and clinical indicators in nt3434A→G family were analyzed. RESULTS: nt3434A→G mutation was detected in one diabetic patient but not found in NC group...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#11
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28461337/the-mitochondrial-outer-membrane-protein-mitoneet-is-a-redox-enzyme-catalyzing-electron-transfer-from-fmnh2-to-oxygen-or-ubiquinone
#12
COMPARATIVE STUDY
Yiming Wang, Aaron P Landry, Huangen Ding
Increasing evidence suggests that mitoNEET, a target of the type II diabetes drug pioglitazone, is a key regulator of energy metabolism in mitochondria. MitoNEET is anchored to the mitochondrial outer membrane via its N-terminal α helix domain and hosts a redox-active [2Fe-2S] cluster in its C-terminal cytosolic region. The mechanism by which mitoNEET regulates energy metabolism in mitochondria, however, is not fully understood. Previous studies have shown that mitoNEET specifically interacts with the reduced flavin mononucleotide (FMNH2) and that FMNH2 can quickly reduce the mitoNEET [2Fe-2S] clusters...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28385612/inhibition-of-liver-alanine-aminotransferase-and-aspartate-aminotransferase-by-hesperidin-and-its-aglycone-hesperetin-an-in-vitro-and-in-silico-study
#13
COMPARATIVE STUDY
Sara Zareei, Massoud M A Boojar, Massoud Amanlou
AIMS: This study aimed to investigate the inhibitory effects of two natural flavonoids, hesperetin (HT) and hesperidin (HD), on two gluconeogenesis enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and their possible mechanisms of action. MAIN METHODS: Rat liver incubated with different concentrations of HT and HD was used to measure enzyme activities spectrophotometrically, based on monitoring the oxidation of NADH to NAD(+) at 340nm...
June 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28303408/methylene-blue-decreases-mitochondrial-lysine-acetylation-in-the-diabetic-heart
#14
Jessica M Berthiaume, Chia-Heng Hsiung, Alison B Austin, Sean P McBrayer, Mikayla M Depuydt, Margaret P Chandler, Masaru Miyagi, Mariana G Rosca
Diabetic cardiomyopathy is preceded by mitochondrial alterations, and progresses to heart failure. We studied whether treatment with methylene blue (MB), a compound that was reported to serve as an alternate electron carrier within the mitochondrial electron transport chain (ETC), improves mitochondrial metabolism and cardiac function in type 1 diabetes. MB was administered at 10 mg/kg/day to control and diabetic rats. Both echocardiography and hemodynamic studies were performed to assess cardiac function...
August 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28289409/mitochondrial-dna-activates-the-nlrp3-inflammasome-and-predisposes-to-type-1-diabetes-in-murine-model
#15
Daniela Carlos, Frederico R C Costa, Camila A Pereira, Fernanda A Rocha, Juliana N U Yaochite, Gabriela G Oliveira, Fernando S Carneiro, Rita C Tostes, Simone G Ramos, Dario S Zamboni, Niels O S Camara, Bernhard Ryffel, João S Silva
Although a correlation between polymorphisms of NOD-like receptor family-pyrin domain containing 3 (NLRP3) and predisposition to type 1 diabetes (T1D) has been identified, the potential function and activation of the NLRP3 inflammasome in T1D have not been clarified. The present study shows that non-obese diabetic mice exhibited increased NLRP3, and pro-IL-1β gene expression in pancreatic lymph nodes (PLNs). Similar increases in gene expression of NLRP3, apoptosis associated speck like protein (ASC) and pro-IL-1β were induced by multiple low doses of streptozotocin (STZ) in C57BL/6 mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#16
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
April 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27923678/flavin-nucleotides-act-as-electron-shuttles-mediating-reduction-of-the-2fe-2s-clusters-in-mitochondrial-outer-membrane-protein-mitoneet
#17
Aaron P Landry, Yiming Wang, Zishuo Cheng, Robert B Crochet, Yong-Hwan Lee, Huangen Ding
MitoNEET, a primary target of type II diabetes drug pioglitazone, has an essential role in regulating energy metabolism, iron homeostasis, and production of reactive oxygen species in mitochondria. Structurally, mitoNEET is anchored to the mitochondrial outer membrane via its N-terminal transmembrane α-helix. The C-terminal cytosolic domain of mitoNEET hosts a redox active [2Fe-2S] cluster via three cysteine and one histidine residues. Here we report that the reduced flavin nucleotides can rapidly reduce the mitoNEET [2Fe-2S] clusters under anaerobic or aerobic conditions...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27888691/redox-imbalance-and-mitochondrial-abnormalities-in-the-diabetic-lung
#18
Jinzi Wu, Zhen Jin, Liang-Jun Yan
Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD(+) redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/27874078/glutamate-dehydrogenase-activator-bch-stimulating-reductive-amination-prevents-high-fat-high-fructose-diet-induced-steatohepatitis-and-hyperglycemia-in-c57bl-6j-mice
#19
Seung Jin Han, Sung-E Choi, Sang-A Yi, Jong Gab Jung, Ik-Rak Jung, Maureen Shin, Seok Kang, Hyunhee Oh, Hae Jin Kim, Dae Jung Kim, Ji Eun Kwon, Cheol Soo Choi, Kwan Woo Lee, Yup Kang
Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27592202/tissue-specific-regulation-of-sirtuin-and-nicotinamide-adenine-dinucleotide-biosynthetic-pathways-identified-in-c57bl-6-mice-in-response-to-high-fat-feeding
#20
Janice E Drew, Andrew J Farquharson, Graham W Horgan, Lynda M Williams
The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks. An in-house custom-designed multiplex gene expression assay assessed all 7 mouse SIRTs (SIRT1-7) and 16 enzymes involved in conversion of tryptophan, niacin, nicotinamide riboside and metabolic precursors to NAD...
August 14, 2016: Journal of Nutritional Biochemistry
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