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NADH AND diabetes

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https://www.readbyqxmd.com/read/28598104/-association-of-nt3434a-8594-g-mutation-in-mitochondrial-dna-nd1-gene-with-diabetes-mellitus
#1
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
#2
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
#3
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
#4
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
#5
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...
March 16, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27561726/assessment-of-metformin-induced-changes-in-cardiac-and-hepatic-redox-state-using-hyperpolarized-1-13c-pyruvate
#12
Andrew J M Lewis, Jack J J Miller, Chloe McCallum, Oliver J Rider, Stefan Neubauer, Lisa C Heather, Damian J Tyler
Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-(13)C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment on heart and liver pyruvate metabolism in rats in vivo. Both oral treatment for 4 weeks and a single intravenous metformin infusion significantly increased the cardiac [1-(13)C]lactate:[1-(13)C]pyruvate ratio but had no effect on the [1-(13)C]bicarbonate + (13)CO2:[1-(13)C]pyruvate ratio, an index of pyruvate dehydrogenase flux...
December 2016: Diabetes
https://www.readbyqxmd.com/read/27519271/investigating-mitochondrial-redox-state-using-nadh-and-nadph-autofluorescence
#13
REVIEW
Thomas S Blacker, Michael R Duchen
The redox states of the NAD and NADP pyridine nucleotide pools play critical roles in defining the activity of energy producing pathways, in driving oxidative stress and in maintaining antioxidant defences. Broadly speaking, NAD is primarily engaged in regulating energy-producing catabolic processes, whilst NADP may be involved in both antioxidant defence and free radical generation. Defects in the balance of these pathways are associated with numerous diseases, from diabetes and neurodegenerative disease to heart disease and cancer...
November 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27474326/optical-isopropanol-biosensor-using-nadh-dependent-secondary-alcohol-dehydrogenase-s-adh
#14
Po-Jen Chien, Ming Ye, Takuma Suzuki, Koji Toma, Takahiro Arakawa, Yasuhiko Iwasaki, Kohji Mitsubayashi
Isopropanol (IPA) is an important solvent used in industrial activity often found in hospitals as antiseptic alcohol rub. Also, IPA may have the potential to be a biomarker of diabetic ketoacidosis. In this study, an optical biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH) for IPA measurement was constructed and evaluated. An ultraviolet light emitting diode (UV-LED, λ=340nm) was employed as the excitation light to excite nicotinamide adenine dinucleotide (NADH). A photomultiplier tube (PMT) was connected to a two-way branch optical fiber for measuring the fluorescence emitted from the NADH...
October 1, 2016: Talanta
https://www.readbyqxmd.com/read/27337687/autophagy-deficiency-in-myeloid-cells-increases-susceptibility-to-obesity-induced-diabetes-and-experimental-colitis
#15
Hae-Youn Lee, Jinyoung Kim, Wenying Quan, June-Chul Lee, Min-Soo Kim, Seok-Hyung Kim, Jin-Woo Bae, Kyu Yeon Hur, Myung-Shik Lee
Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue...
August 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27274295/sources-and-implications-of-nadh-nad-redox-imbalance-in-diabetes-and-its-complications
#16
REVIEW
Jinzi Wu, Zhen Jin, Hong Zheng, Liang-Jun Yan
NAD(+) is a fundamental molecule in metabolism and redox signaling. In diabetes and its complications, the balance between NADH and NAD(+) can be severely perturbed. On one hand, NADH is overproduced due to influx of hyperglycemia to the glycolytic and Krebs cycle pathways and activation of the polyol pathway. On the other hand, NAD(+) can be diminished or depleted by overactivation of poly ADP ribose polymerase that uses NAD(+) as its substrate. Moreover, sirtuins, another class of enzymes that also use NAD(+) as their substrate for catalyzing protein deacetylation reactions, can also affect cellular content of NAD(+)...
2016: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/27255381/mechanisms-of-doxorubicin-toxicity-in-pancreatic-%C3%AE-cells
#17
Emma A Heart, Shpetim Karandrea, Xiaomei Liang, Maren E Balke, Patrick A Beringer, Elyse M Bobczynski, Delaine Zayas-Bazán Burgos, Tiffany Richardson, Joshua P Gray
Exposure to chemotherapeutic agents has been linked to an increased risk of type 2 diabetes (T2D), a disease characterized by both the peripheral insulin resistance and impaired glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Using the rat β-cell line INS-1 832/13 and isolated mouse pancreatic islets, we investigated the effect of the chemotherapeutic drug doxorubicin (Adriamycin) on pancreatic β-cell survival and function. Exposure of INS-1 832/13 cells to doxorubicin caused impairment of GSIS, cellular viability, an increase in cellular toxicity, as soon as 6 h post-exposure...
August 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27188291/loss-of-ncb5or-in-the-cerebellum-disturbs-iron-pathways-potentiates-behavioral-abnormalities-and-exacerbates-harmaline-induced-tremor-in-mice
#18
Matthew A Stroh, Michelle K Winter, Russell H Swerdlow, Kenneth E McCarson, Hao Zhu
Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain...
August 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/26989452/exercise-training-attenuates-upregulation-of-p47-phox-and-p67-phox-in-hearts-of-diabetic-rats
#19
Neeru M Sharma, Brandon Rabeler, Hong Zheng, Eugenia Raichlin, Kaushik P Patel
Exercise training (ExT) is currently being used as a nonpharmacological strategy to improve cardiac function in diabetic patients. However, the molecular mechanism(s) underlying its beneficial effects remains poorly understood. Oxidative stress is known to play a key role in the pathogenesis of diabetic cardiomyopathy and one of the enzyme systems that produce reactive oxygen species is NADH/NADPH oxidase. The goal of this study was to investigate the effect of streptozotocin- (STZ-) induced diabetes on expression of p47(phox) and p67(phox), key regulatory subunits of NADPH oxidase, in cardiac tissues and determine whether ExT can attenuate these changes...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/26979549/beta-cell-mitochondrial-carriers-and-the-diabetogenic-stress-response
#20
REVIEW
Thierry Brun, Pierre Maechler
Mitochondria play a central role in pancreatic beta-cells by coupling metabolism of the secretagogue glucose to distal events of regulated insulin exocytosis. This process requires transports of both metabolites and nucleotides in and out of the mitochondria. The molecular identification of mitochondrial carriers and their respective contribution to beta-cell function have been uncovered only recently. In type 2 diabetes, mitochondrial dysfunction is an early event and may precipitate beta-cell loss. Under diabetogenic conditions, characterized by glucotoxicity and lipotoxicity, the expression profile of mitochondrial carriers is selectively modified...
October 2016: Biochimica et Biophysica Acta
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