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NADH AND diabetes

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https://www.readbyqxmd.com/read/29142401/phytochemical-compositions-and-in-vitro-assessments-of-antioxidant-and-antidiabetic-potentials-of-fractions-from-ehretia-cymosa-thonn
#1
Akintayo Ogundajo, Anofi Tom Ashafa
Background: Ehretia cymosa Thonn. is a popular medicinal plant used in different parts of West Africa for the treatment of various ailments including diabetes mellitus. Objective: The current study investigates bioactive constituents and in vitro antioxidant and antidiabetic potentials of fractions from extract of E. cymosa. Materials and Methods: Phytochemical investigation and antioxidant assays were carried out using standard procedures...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#2
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120608/biochemical-gas-sensors-biosniffers-using-forward-and-reverse-reactions-of-secondary-alcohol-dehydrogenase-for-breath-isopropanol-and-acetone-as-potential-volatile-biomarkers-of-diabetes-mellitus
#3
Po-Jen Chien, Takuma Suzuki, Masato Tsujii, Ming Ye, Isao Minami, Kanako Toda, Hiromi Otsuka, Koji Toma, Takahiro Arakawa, Kouji Araki, Yasuhiko Iwasaki, Kayoko Shinada, Yoshihiro Ogawa, Kohji Mitsubayashi
This study describes two biosniffers to determine breath acetone and isopropanol (IPA) levels and applies them for breath measurement in healthy subjects and diabetic patients. Secondary alcohol dehydrogenase (S-ADH) can reduce acetone and oxidize nicotinamide adenine dinucleotide (NADH to NAD(+)) in a weak acid environment. NADH can be excited by 340 nm excitation lights and subsequently emit 490 nm fluorescence. Therefore, acetone can be measured by the decrease in NADH fluorescence intensity. S-ADH can also oxidize IPA and reduce NAD(+) to NADH when it is in an alkaline environment...
November 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#4
Wo-Lin Hou, Jun Yin, Miriayi Alimujiang, Xue-Ying Yu, Li-Gen Ai, Yu-Qian Bao, Fang Liu, Wei-Ping Jia
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29104634/endogenous-nampt-upregulation-is-associated-with-diabetic-nephropathy-inflammatory-fibrosis-through-the-nf-%C3%AE%C2%BAb-p65-and-sirt1-pathway-nmn-alleviates-diabetic-nephropathy-inflammatory-fibrosis-by-inhibiting-endogenous-nampt
#5
Ye Chen, Yuzhen Liang, Tingting Hu, Riming Wei, Congjie Cai, Ping Wang, Lingyu Wang, Wei Qiao, Leping Feng
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD(+)) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29095437/metformin-ameliorates-arsenic-trioxide-hepatotoxicity-via-inhibiting-mitochondrial-complex-i
#6
Sunbin Ling, Qiaonan Shan, Peng Liu, Tingting Feng, Xuanyu Zhang, Penghui Xiang, Kangchen Chen, Haiyang Xie, Penghong Song, Lin Zhou, Jimin Liu, Shusen Zheng, Xiao Xu
Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29089371/fxr-tgr5-dual-agonist-prevents-progression-of-nephropathy-in-diabetes-and-obesity
#7
Xiaoxin X Wang, Dong Wang, Yuhuan Luo, Komuraiah Myakala, Evgenia Dobrinskikh, Avi Z Rosenberg, Jonathan Levi, Jeffrey B Kopp, Amanda Field, Ashley Hill, Scott Lucia, Liru Qiu, Tao Jiang, Yingqiong Peng, David Orlicky, Gabriel Garcia, Michal Herman-Edelstein, Vivette D'Agati, Kammi Henriksen, Luciano Adorini, Mark Pruzanski, Cen Xie, Kristopher W Krausz, Frank J Gonzalez, Suman Ranjit, Alexander Dvornikov, Enrico Gratton, Moshe Levi
Bile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db mice with type 2 diabetes, and C57BL/6J mice with high-fat diet-induced obesity...
October 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29073779/mitochondrial-nad-nadh-redox-state-and-diabetic-cardiomyopathy
#8
Jessica M Berthiaume, Jacob G Kurdys, Danina M Muntean, Mariana G Rosca
SIGNIFICANCE: Diabetic cardiomyopathy is a frequent complication occurring even in well-controlled asymptomatic diabetic patients, and may advance to heart failure. Recent advances: The diabetic heart is characterized by a state of "metabolic rigidity" involving enhanced rates of fatty acid uptake and mitochondrial oxidation as the predominant energy source, and exhibits mitochondrial electron transport chain defects. These alterations promote redox state changes evidenced by a decreased NAD+/NADH ratio associated with an increase in acetyl-CoA/CoA ratio...
October 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29050400/metformin-reverses-trap1-mutation-associated-alterations-in-mitochondrial-function-in-parkinson-s-disease
#9
Julia C Fitzgerald, Alexander Zimprich, Daniel A Carvajal Berrio, Kevin M Schindler, Brigitte Maurer, Claudia Schulte, Christine Bus, Anne-Kathrin Hauser, Manuela Kübler, Rahel Lewin, Dheeraj Reddy Bobbili, Lisa M Schwarz, Evangelia Vartholomaiou, Kathrin Brockmann, Richard Wüst, Johannes Madlung, Alfred Nordheim, Olaf Riess, L Miguel Martins, Enrico Glaab, Patrick May, Katja Schenke-Layland, Didier Picard, Manu Sharma, Thomas Gasser, Rejko Krüger
The mitochondrial proteins TRAP1 and HTRA2 have previously been shown to be phosphorylated in the presence of the Parkinson's disease kinase PINK1 but the downstream signalling is unknown. HTRA2 and PINK1 loss of function causes parkinsonism in humans and animals. Here, we identified TRAP1 as an interactor of HTRA2 using an unbiased mass spectrometry approach. In our human cell models, TRAP1 overexpression is protective, rescuing HTRA2 and PINK1-associated mitochondrial dysfunction and suggesting that TRAP1 acts downstream of HTRA2 and PINK1...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28980425/investigating-the-healing-mechanisms-of-an-angiogenesis-promoting-topical-treatment-for-diabetic-wounds-using-multimodal-microscopy
#10
Joanne Li, Andrew J Bower, Zane Arp, Eric J Olson, Claire Holland, Eric J Chaney, Marina Marjanovic, Paritosh Pande, Aneesh Alex, Stephen A Boppart
Impaired skin wound healing is a significant comorbid condition of diabetes that is caused by poor microcirculation, among other factors. Studies have shown that angiogenesis, a critical step in the wound healing process in diabetic wounds, can be promoted under hypoxia. In this study, an angiogenesis-promoting topical treatment for diabetic wounds, which promotes angiogenesis by mimicking a hypoxic environment via inhibition of prolyl hydroxylase resulting in elevation or maintenance of hypoxia-inducible factor, was investigated utilizing a custom-built multimodal microscopy system equipped with phase-variance optical coherence tomography (PV-OCT) and fluorescence lifetime imaging microscopy (FLIM)...
October 5, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28973657/in-vitro-characterization-of-mitochondrial-function-and-structure-in-rat-and-human-cells-with-a-deficiency-of-the-nadh-ubiquinone-oxidoreductase-ndufc2-subunit
#11
Salvatore Raffa, Cristina Scrofani, Sabatino Valente, Andrea Micaloni, Forte Maurizio, Franca Bianchi, Roberta Coluccia, Aron M Geurts, Sebastiano Sciarretta, Massimo Volpe, Maria Rosaria Torrisi, Speranza Rubattu
Ndufc2, a subunit of the NADH:ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage...
August 30, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28950020/thymoquinone-ameliorates-diabetic-phenotype-in-diet-induced-obesity-mice-via-activation-of-sirt-1-dependent-pathways
#12
Shpetim Karandrea, Huquan Yin, Xiaomei Liang, Angela L Slitt, Emma A Heart
Thymoquinone, a natural occurring quinone and the main bioactive component of plant Nigella sativa, undergoes intracellular redox cycling and re-oxidizes NADH to NAD+. TQ administration (20 mg/kg/bw/day) to the Diet-Induced Obesity (DIO) mice reduced their diabetic phenotype by decreasing fasting blood glucose and fasting insulin levels, and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose and insulin tolerance tests (OGTT and ITT). Furthermore, TQ decreased serum cholesterol levels and liver triglycerides, increased protein expression of phosphorylated Akt, decreased serum levels of inflammatory markers resistin and MCP-1, and decreased NADH/NAD+ ratio...
2017: PloS One
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
November 2017: Kidney International
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