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NAD+ AND Insulin

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https://www.readbyqxmd.com/read/28820880/knock-out-of-a-mitochondrial-sirtuin-protects-neurons-from-degeneration-in-caenorhabditis-elegans
#1
Rachele Sangaletti, Massimo D'Amico, Jeff Grant, David Della-Morte, Laura Bianchi
Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis...
August 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28751004/polyphenols-activate-energy-sensing-network-in-insulin-resistant-models
#2
Radika Mutlur Krishnamoorthy, Anuradha Carani Venkatraman
Unhealthy diet deficient in fruits and vegetables but rich in calories is considered to be one factor responsible for the increased prevalence of insulin resistance and type 2 diabetes (T2D). The consumption of fast foods and soft drinks increases fructose consumption per se and this is of major concern since prolonged fructose intake induces insulin resistance and thereby T2D. The energy homeostasis is regulated by a network consisting of "fuel gauze" called AMP-activated protein kinase (AMPK), the NAD(+) dependent type III deacetylase (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) which is disrupted in T2D...
July 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28736243/from-insulin-synthesis-to-secretion-alternative-splicing-of-type-2-ryanodine-receptor-gene-is-essential-for-insulin-secretion-in-pancreatic-%C3%AE-cells
#3
Hiroshi Okamoto, Shin Takasawa, Yasuhiko Yamamoto
Increases in the intracellular Ca(2+) concentration in pancreatic islets, resulting from the its mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca(2+) mobilizing second messenger synthesized from NAD(+) by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75...
July 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#4
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28693571/characterization-of-erythrose-reductase-from-yarrowia-lipolytica-and-its-influence-on-erythritol-synthesis
#5
Tomasz Janek, Adam Dobrowolski, Anna Biegalska, Aleksandra M Mirończuk
BACKGROUND: Erythritol is a natural sweetener that is used in the food industry. It is produced as an osmoprotectant by bacteria and yeast. Due to its chemical properties, it does not change the insulin level in the blood, and therefore it can be safely used by diabetics. Previously, it has been shown that erythrose reductase (ER), which catalyzes the final step, plays a crucial role in erythritol synthesis. ER reduces erythrose to erythritol with NAD(P)H as a cofactor. Despite many studies on erythritol synthesis by Yarrowia lipolytica, the enzymes involved in this metabolic pathway have ever been described...
July 11, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28688179/resveratrol-attenuates-excessive-ethanol-exposure-induced-insulin-resistance-in-rats-via-improving-nad-nadh-ratio
#6
Gang Luo, Bingqing Huang, Xiang Qiu, Lin Xiao, Ning Wang, Qin Gao, Wei Yang, Liping Hao
SCOPE: Resveratrol has been shown to improve insulin resistance via activating the NAD(+) -dependent deacetylase SIRT1, but the effects of resveratrol on ethanol-induced insulin resistance remain unclear. This study was designed to explore the potential mechanism by which resveratrol ameliorated ethanol-induced insulin resistance, focusing on its regulations on the ratio of NAD(+) /NADH and SIRT1 expression. METHODS AND RESULTS: Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 0...
July 8, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28678523/nutritional-biomarkers-current-view-and-future-perspectives
#7
Shubhra Pande, Valentina A Kratasyuk, Nadezhda N Medvedeva, Oxana A Kolenchukova, Alla B Salmina
There is a poor relationship between nutrient intake and existing nutritional biomarkers due to variety of factors affecting their sensitivity and specificity. To explore the impact of nutrients at molecular level and devising a sensitive biomarker, proteomics is a central technology with sirtuins as one of the most promising nutritional biomarker. Sirtuins (seven mammalian sirtuins reported so far), have been reported to perform protein deacetylases and ADP-ribosyltransferases activity. It is distributed in different cellular compartments thereby controlling several metabolic processes...
July 5, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28655753/the-thermodynamic-basis-of-glucose-stimulated-insulin-release-a-model-of-the-core-mechanism
#8
David F Wilson, Abigail T J Cember, Franz M Matschinsky
A model for glucose sensing by pancreatic β-cells is developed and compared with the available experimental data. The model brings together mathematical representations for the activities of the glucose sensor, glucokinase, and oxidative phosphorylation. Glucokinase produces glucose 6-phosphate (G-6-P) in an irreversible reaction that determines glycolytic flux. The primary products of glycolysis are NADH and pyruvate. The NADH is reoxidized and the reducing equivalents transferred to oxidative phosphorylation by the glycerol phosphate shuttle, and some of the pyruvate is oxidized by pyruvate dehydrogenase and enters the citric acid cycle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28649105/-aging-and-homeostasis-age-associated-diseases-and-clinical-application-of-nmn-nicotinamide-mononucleotide
#9
Junichiro Irie, Hiroshi Itoh
Sirtuins are NAD(+)-dependent deacetylase and have drawn much attention as important regulators of aging and longevity. Because NAD(+) decline during the aging process, the approach to regulating aging using NAD(+) precursor such as nicotinamide mononucleotide (NMN) to replenish cellular NAD(+) through the activation of sirtuins have been investigated. In various animal models, NMN has been shown to mitigate age-associated physiological changes in liver, adipose tissue, muscle, pancreas, kidney, retina, and central nerve system...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28614912/peroxisome-proliferator-activated-receptor-%C3%AE-facilitates-osteogenic-differentiation-in-mc3t3-e1-cells-via-the-sirtuin-1-dependent-signaling-pathway
#10
Kai Gong, Bo Qu, Cairu Wang, Jingsong Zhou, Dongfa Liao, Wei Zheng, Xianming Pan
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a NAD(+)-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) γ. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPARβ/δ-dependent manner...
June 30, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28591806/quantitative-proteomics-of-intestinal-mucosa-from-male-mice-lacking-intestinal-epithelial-insulin-receptors
#11
Stina Rikke Jensen, Erwin M Schoof, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Thomas Kislinger, Patricia L Brubaker
The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was applied to jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28584577/antioxidant-mechanism-of-black-garlic-extract-involving-nuclear-factor-erythroid-2-like-factor-2-pathway
#12
Ae Wha Ha, Woo Kyoung Kim
BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0...
June 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28575743/igf-ii-promotes-neuroprotection-and-neuroplasticity-recovery-in-a-long-lasting-model-of-oxidative-damage-induced-by-glucocorticoids
#13
E Martín-Montañez, C Millon, F Boraldi, F Garcia-Guirado, C Pedraza, E Lara, L J Santin, J Pavia, M Garcia-Fernandez
Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT)...
May 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28544355/temporal-overexpression-of-sirt1-in-skeletal-muscle-of-adult-mice-does-not-improve-insulin-sensitivity-or-markers-of-mitochondrial-biogenesis
#14
Kristoffer Svensson, Samuel A LaBarge, Vitor F Martins, Simon Schenk
AIMS: Activation of the NAD(+) dependent protein deacetylase SIRT1 has been proposed as a therapeutic strategy to treat mitochondrial dysfunction and insulin resistance in skeletal muscle. However, life-long overexpression of SIRT1 in skeletal muscle does not improve parameters of mitochondrial function and insulin sensitivity. In this study we investigated whether temporal overexpression of SIRT1 in muscle of adult mice would affect skeletal muscle mitochondrial function and insulin sensitivity...
May 22, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28543688/glycated-human-albumin-alters-mitochondrial-respiration-in-preadipocyte-3t3-l1-cells
#15
Pascal Baret, Fanny Le Sage, Cynthia Planesse, Olivier Meilhac, Anne Devin, Emmanuel Bourdon, Philippe Rondeau
Diabetes and obesity are strongly associated with increased levels of circulating advanced glycation end products (AGEs) and reactive oxygen species (ROS). These two molecular phenomena affect the physiology of adipose tissue, a biological driver of the metabolic syndrome, leading to an inflammatory profile and insulin resistance, which could contribute to obesity/diabetes-associated complications, such as cardiovascular diseases. Herein, we investigated the impact of AGEs on mitochondrial bioenergetics in murine preadipocyte cells (3T3-L1) and cellular redox homeostasis...
May 22, 2017: BioFactors
https://www.readbyqxmd.com/read/28540469/a-3d-microfluidic-perfusion-system-made-from-glass-for-multiparametric-analysis-of-stimulus-secretioncoupling-in-pancreatic-islets
#16
Torben Schulze, Kai Mattern, Eike Früh, Lars Hecht, Ingo Rustenbeck, Andreas Dietzel
Microfluidic perfusion systems (MPS) are well suited to perform multiparametric measurements with small amounts of tissue to function as an Organ on Chip device (OOC). Such microphysiolgical characterization is particularly valuable in research on the stimulus-secretion-coupling of pancreatic islets. Pancreatic islets are fully functional competent mini-organs, which serve as fuel sensors and transduce metabolic activity into rates of hormone secretion. To enable the simultaneous measurement of fluorescence and oxygen consumption we designed a microfluidic perfusion system from borosilicate glass by 3D femtosecond laser ablation...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#17
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/28440735/nuclear-factor-e2-related-factor-2-knockdown-enhances-glucose-uptake-and-alters-glucose-metabolism-in-aml12-hepatocytes
#18
Xiaoyang Yuan, Huijing Huang, Yi Huang, Jinli Wang, Jinhua Yan, Ling Ding, Cuntai Zhang, Le Zhang
Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P < 0.05) of that of untransfected control cells...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28435063/regulation-of-nampt-expression-by-transcriptional-coactivator-ncoa6-in-pancreatic-%C3%AE-cells
#19
Jin Yoon, Kyung Jin Lee, Gyun-Sik Oh, Geun Hyang Kim, Seung-Whan Kim
Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator and crucial for insulin secretion and glucose metabolism in pancreatic β-cells. However, the regulatory mechanism of β-cell function by NCOA6 is largely unknown. In this study, we found that the transcript levels of nicotinamide phosphoribosyltransferase (Nampt) were decreased in islets of NCOA6(+/-) mice compared with NCOA6(+/+) mice. Moreover, NCOA6 overexpression increased the levels of Nampt transcripts in the mouse pancreatic β-cell line NIT-1...
June 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28380376/sirt4-is-a-lysine-deacylase-that-controls-leucine-metabolism-and-insulin-secretion
#20
Kristin A Anderson, Frank K Huynh, Kelsey Fisher-Wellman, J Darren Stuart, Brett S Peterson, Jonathan D Douros, Gregory R Wagner, J Will Thompson, Andreas S Madsen, Michelle F Green, R Michael Sivley, Olga R Ilkayeva, Robert D Stevens, Donald S Backos, John A Capra, Christian A Olsen, Jonathan E Campbell, Deborah M Muoio, Paul A Grimsrud, Matthew D Hirschey
Sirtuins are NAD(+)-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic. Using a combination of phylogenetics, structural biology, and enzymology, we show that SIRT4 removes three acyl moieties from lysine residues: methylglutaryl (MG)-, hydroxymethylglutaryl (HMG)-, and 3-methylglutaconyl (MGc)-lysine...
April 4, 2017: Cell Metabolism
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