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NAD+ AND Insulin

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https://www.readbyqxmd.com/read/29756464/glucose-acutely-reduces-cytosolic-and-mitochondrial-h-sub-2-sub-o-sub-2-sub-in-rat-pancreatic-beta-cells
#1
Jean-Philippe Deglasse, Leticia Prates Roma, Daniel Pastor-Flores, Patrick Gilon, Tobias P Dick, Jean-Christophe Jonas
AIMS: Whether H<sub>2</sub>O<sub>2</sub> contributes to the glucose-dependent stimulation of insulin secretion by pancreatic β-cells is highly controversial. We used two H<sub>2</sub>O<sub>2</sub>-sensitive probes, roGFP2-Orp1 and HyPer with its pH-control SypHer, to test the acute effects of glucose, monomethylsuccinate, leucine with glutamine, and α-ketoisocaproate, on β-cell cytosolic and mitochondrial H<sub>2</sub>O<sub>2</sub> concentrations...
May 14, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29678570/overexpression-of-nrk1-ameliorates-diet-and-age-induced-hepatic-steatosis-and-insulin-resistance
#2
Rui Fan, Jing Cui, Feng Ren, Qingzhi Wang, Yanmei Huang, Bin Zhao, Lai Wei, Xinlai Qian, Xiwen Xiong
NAD+ is a co-enzyme in redox reactions and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we sought to identify the roles of nicotinamide riboside kinase 1 (NRK1) plays in regulating hepatic NAD+ biosynthesis and lipid metabolism...
June 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29671950/comparative-transcriptomics-across-14-drosophila-species-reveals-signatures-of-longevity
#3
Siming Ma, Andrei S Avanesov, Emily Porter, Byung Cheon Lee, Marco Mariotti, Nadezhda Zemskaya, Roderic Guigo, Alexey A Moskalev, Vadim N Gladyshev
Lifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life-history traits and transcriptomes of 14 Drosophila species differing more than sixfold in lifespan, we explored expression divergence and identified genes and processes that correlate with longevity. These longevity signatures suggested that longer-lived flies upregulate fatty acid metabolism, downregulate neuronal system development and activin signaling, and alter dynamics of RNA splicing...
April 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29535637/the-role-of-sirt6-in-obesity-and-diabetes
#4
REVIEW
Jiangying Kuang, Lei Chen, Qin Tang, Jinhang Zhang, Yanping Li, Jinhan He
Sirt6 is one of the sirtuin family members, a kind of NAD+-dependent histone deacetylase and ADP-ribose transferase enzyme. It has an important role in physiological and pathological processes, regulating aging, cancer, obesity, insulin resistance, inflammation, and energy metabolism. Recent studies have suggested that reduced Sirt6 action is related to obesity and diabetes. Aging and overnutrition, two major risk factors for obesity and diabetes, lead to decreased Sirt6 level and function, which results in abnormal glucose and lipid metabolism...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29535407/size-exclusion-chromatography-method-for-purification-of-nicotinamide-mononucleotide-nmn-from-bacterial-cells
#5
George Cătălin Marinescu, Roua-Gabriela Popescu, Anca Dinischiotu
Over 12% of the world's health resources are spent on treating diabetes, as high blood glucose is the third cause of mortality worldwide. Insulin resistance is the basis of the most common form of diabetes: type 2 diabetes. Recent animal studies report successful attempts at reversing type 2 diabetes by the administering of the NAD+ precursor nicotinamide mononucleotide (NMN). However, the current high price of this molecule urges for more efficient and cost-effective production methods. This work proposes a method for purifying NMN by Size Exclusion Chromatography (SEC) on silica with a covalently attached coating of poly(2-hydroxyethyl aspartamide) (PolyHEA) stationary phase using an isocratic elution with a denaturing mobile phase (50 mM formic acid) from a complex molecular mixture such as a fermentation broth...
March 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29524414/a-novel-sirt1-activator-e6155-improves-insulin-sensitivity-in-type-2-diabetic-kka-y-mice
#6
Peng Liu, Tingting Feng, Xuan Zuo, Xiao Wang, Jinque Luo, Ni Li, Xiaowan Han, Ningyu Zhu, Suowen Xu, Yanni Xu, Zheng Gen Jin, Shuyi Si
Sirtuin 1 (SIRT1) is an NAD+ -dependent protein deacetylase that plays a critical role in controlling energy metabolism, stress response and aging. Hence, enhancing SIRT1 activity could be a potential therapeutic strategy to treat metabolic diseases such as diabetes. However, pharmacological activators for SIRT1 are scarce to date. In this study, using the optimized high throughput screening, we identified E6155, a piperazine 1, 4- diamide compound, as a new small molecular activator of SIRT1. We further found that E6155 significantly upregulated glucose uptake in cultured normal liver cells and skeletal muscle cells through increasing SIRT1 deacetylase activity...
April 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29435415/the-postpartum-effect-of-maternal-diabetes-on-the-circulating-levels-of-sirtuins-and-superoxide-dismutase
#7
Samar Sultan, Nada Alzahrani, Kalthoom Al-Sakkaf
Gestational diabetes mellitus (GDM) is a glucose intolerance disorder which occurs during pregnancy as a result of insulin insensitivity; it usually disappears after delivery. However, some women with GDM can develop type 2 diabetes (T2D) after delivery, and the mechanisms by which this occurs remain unknown. This study compared the levels of sirtuins (NAD-dependent deacetylases) and antioxidative enzymes in postpartum women with previous GDM (pGDM) or T2D and in postpartum women with a previous healthy pregnancy (controls)...
February 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29402742/novel-sirt1-activator-mhy2233-improves-glucose-tolerance-and-reduces-hepatic-lipid-accumulation-in-db-db-mice
#8
Min Jo Kim, Hye Jin An, Dae Hyun Kim, Bonggi Lee, Hye Jin Lee, Sultan Ullah, Su Jeong Kim, Hyoung Oh Jeong, Kyoung Mi Moon, Eun Kyeong Lee, Jungho Yang, Jinia Akter, Pusoon Chun, Hyung Ryong Moon, Hae Young Chung
The NAD+ -dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720. We performed an in vitro SIRT1 activity assay to identify the strongest SIRT1 activator...
February 15, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29371109/functional-genetic-variants-within-the-sirt2-gene-promoter-in-type-2-diabetes-mellitus
#9
Tingting Liu, Wentao Yang, Shuchao Pang, Shipeng Yu, Bo Yan
AIMS: Type 2 diabetes mellitus (T2D) is a common and complex metabolic diseases caused by interactions between environmental and genetic factors. Genome-wide association studies have identified more than 80 common genetic variants for T2D, which account for only ∼10% of the heritability of T2D cases. SIRT2, a member of NAD(+)-dependent class III deacetylases, is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy. In maintaining metabolic homeostasis, SIRT2 regulates adipocyte differentiation, fatty acid oxidation, gluconeogenesis, and insulin sensitivity...
March 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#10
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29330025/the-role-of-extracellular-and-intracellular-nicotinamide-phosphoribosyl-transferase-in-cancer-diagnostic-and-therapeutic-perspectives-and-challenges
#11
REVIEW
Maria Dalamaga, Gerasimos Socrates Christodoulatos, Christos S Mantzoros
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties...
January 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29242624/plant-derived-compounds-strigolactone-gr24-and-pinosylvin-activate-sirt1-and-enhance-glucose-uptake-in-rat-skeletal-muscle-cells
#12
Shalem Modi, Nagendra Yaluri, Tarja Kokkola, Markku Laakso
Insulin resistance is a characteristic finding in hyperglycaemia and type 2 diabetes. SIRT1 is a NAD+ dependent deacetylase that plays a central role in glucose homeostasis and energy metabolism. SIRT1 activators, including plant polyphenols such as resveratrol, improve insulin sensitivity in skeletal muscle tissue. We hypothesised that the novel plant-derived compounds, strigolactone and pinosylvin, beneficially enhance SIRT1 function, insulin signalling, glucose uptake, and mitochondrial biogenesis in skeletal muscle cells...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146412/skeletal-muscle-overexpression-of-nicotinamide-phosphoribosyl-transferase-in-mice-coupled-with-voluntary-exercise-augments-exercise-endurance
#13
Sheila R Costford, Bram Brouwers, Meghan E Hopf, Lauren M Sparks, Mauro Dispagna, Ana P Gomes, Heather H Cornnell, Chris Petucci, Peter Phelan, Hui Xie, Fanchao Yi, Glenn A Walter, Timothy F Osborne, David A Sinclair, Randall L Mynatt, Julio E Ayala, Stephen J Gardell, Steven R Smith
OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD+ ), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding...
January 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29115468/curcumin-alleviates-liver-oxidative-stress-in-type-1-diabetic-rats
#14
Zhenglu Xie, Binbin Wu, Guozhi Shen, Xiaqing Li, Qianying Wu
The aim of the present study was to determine the effects of curcumin on antioxidants using a rat model of type 1 diabetes. Seven‑week‑old male Sprague‑Dawley rats were injected with Streptozotocin (STZ) intraperitoneally to induce this model, and then treated with 1.0% curcumin (weight ratio) mixed in their diet for 21 days. The present study included three groups: Control group (NC), diabetic rat model group (DC) and a curcumin treated group (Diab‑Cur). The results demonstrated that curcumin treatment markedly decreased the blood glucose levels, plasma malondialdehyde concentration and plasma activity of glutathione peroxidase (GSH‑Px) and catalase (CAT); however, it increased the plasma superoxide dismutase (SOD) and insulin levels...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#15
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...
February 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29069580/nicotinamide-prevents-sweet-beverage-induced-hepatic-steatosis-in-rats-by-regulating-the-g6pd-nadph-nadp-and-gsh-gssg-ratios-and-reducing-oxidative-and-inflammatory-stress
#16
Selene Ángeles Mejía, Luis Arturo Baiza Gutman, Clara Ortega Camarillo, Rafael Medina Navarro, Martha Catalina Sánchez Becerra, Leticia Damasio Santana, Miguel Cruz, Elizabeth Hernández Pérez, Margarita Díaz Flores
The disruption of redox state homeostasis, the overexpression of lipogenic transcription factors and enzymes, and the increase in lipogenic precursors induced by sweetened beverages are determinants of the development of nonalcoholic fatty liver disease. This study evaluated the action of nicotinamide (NAM) on the expression of glucose-6-phosphate dehydrogenase (G6PD) and redox, oxidative, and inflammatory states in a model of nonalcoholic hepatic steatosis induced by high and chronic consumption of carbohydrates...
January 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29043342/antihypertensive-effects-of-tartary-buckwheat-flavonoids-by-improvement-of-vascular-insulin-sensitivity-in-spontaneously-hypertensive-rats
#17
Zuoxu Hou, Yuanyuan Hu, Xingbin Yang, Wensheng Chen
Vascular insulin resistance and oxidative stress contribute to endothelial dysfunction and hypertension. The present study investigated whether chronic treatment with purified Tartary buckwheat flavonoids fraction (TBF) prevents the development of hypertension via improving vascular insulin sensitivity and reducing oxidative stress. Six-week-old male spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) control rats were subjected to different dosages of TBF for 8 weeks. Blood pressure, mesenteric arteriolar vasorelaxation, superoxide anion (O2(-)) generation, NAD(P)H oxidase activity, and insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production were determined...
October 18, 2017: Food & Function
https://www.readbyqxmd.com/read/29031725/intestinal-sirt3-overexpression-in-mice-improves-whole-body-glucose-homeostasis-independent-of-body-weight
#18
Deepti Ramachandran, Rosmarie Clara, Shahana Fedele, Junmin Hu, Endre Lackzo, Jing-Yi Huang, Eric Verdin, Wolfgang Langhans, Abdelhak Mansouri
OBJECTIVE: Intestinal metabolism might play a greater role in regulating whole body metabolism than previously believed. We aimed to enhance enterocyte metabolism in mice and investigate if it plays a role in diet-induced obesity (DIO) and its comorbidities. METHODS: Using the cre-loxP system, we overexpressed the mitochondrial NAD+ dependent protein deacetylase SIRT3 in enterocytes of mice (iSIRT3 mice). We chronically fed iSIRT3 mice and floxed-SIRT3 control (S3fl) mice a low-fat, control diet (CD) or a high-fat diet (HFD) and then phenotyped the mice...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28973648/the-nad-dependent-deacetylase-sirt2-attenuates-oxidative-stress-and-mitochondrial-dysfunction-and-improves-insulin-sensitivity-in-hepatocytes
#19
Vera Lemos, Rita M de Oliveira, Luana Naia, Éva Szegö, Elisabete Ramos, Sónia Pinho, Fernando Magro, Cláudia Cavadas, A Cristina Rego, Vítor Costa, Tiago F Outeiro, Pedro Gomes
Insulin resistance is a major predictor of the development of metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown to exert important metabolic effects, but whether SIRT2 regulates insulin sensitivity in hepatocytes is currently unknown. The aim of this study is to investigate this possibility and to elucidate underlying molecular mechanisms. Here, we show that SIRT2 is downregulated in insulin-resistant hepatocytes and livers, and this was accompanied by increased generation of reactive oxygen species, activation of stress-sensitive ERK1/2 kinase, and mitochondrial dysfunction...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972173/identification-of-the-signals-for-glucose-induced-insulin-secretion-in-ins1-832-13-%C3%AE-cells-using-metformin-induced-metabolic-deceleration-as-a-model
#20
Julien Lamontagne, Anfal Al-Mass, Christopher J Nolan, Barbara E Corkey, S R Murthy Madiraju, Erik Joly, Marc Prentki
Metabolic deceleration in pancreatic β-cells is associated with inhibition of glucose-induced insulin secretion (GIIS), but only in the presence of intermediate/submaximal glucose concentrations. Here, we used acute metformin treatment as a tool to induce metabolic deceleration in INS1 (832/13) β-cells, with the goal of identifying key pathways and metabolites involved in GIIS. Metabolites and pathways previously implicated as signals for GIIS were measured in the cells at 2-25 mm glucose, with or without 5 mm metformin...
November 24, 2017: Journal of Biological Chemistry
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