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NAD+ AND Insulin

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28380376/sirt4-is-a-lysine-deacylase-that-controls-leucine-metabolism-and-insulin-secretion
#7
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
https://www.readbyqxmd.com/read/28375738/sirt3-deficiency-increased-the-vulnerability-of-pancreatic-beta-cells-to-oxidative-stress-induced-dysfunction
#8
Yu Zhou, Arthur C K Chung, Rongrong Fan, Heung Man Lee, Gang Xu, Brian Tomlinson, Juliana C N Chan, Alice P S Kong
AIMS: Hyperlipidemia-induced oxidative stress is considered to be one of the main pathogenic factors that contribute to pancreatic beta cell dysfunction in the development of type 2 diabetes (T2D). Sirtuin 3 (Sirt3) is abundantly expressed in the mitochondria as an NAD(+)-dependent deacetylase and regulates mitochondrial adaptive responses to oxidative stress. We examined the antioxidant defense mechanism of Sirt3 in pancreatic beta cells in the context of hyperlipidemia. RESULTS: Chronic high-fat diet (HFD) feeding caused elevated oxidative stress accompanied by reduced Sirt3 expression in the pancreatic beta cells of wild-type mice...
April 4, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28333148/salusin-%C3%AE-contributes-to-oxidative-stress-and-inflammation-in-diabetic-cardiomyopathy
#9
Ming-Xia Zhao, Bing Zhou, Li Ling, Xiao-Qing Xiong, Feng Zhang, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Salusin-β accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-β levels were increased in diabetic patients. This study was designed to determine whether salusin-β is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-β attenuates cardiac inflammation and oxidative stress in rats with DCM. H9c2 or neonatal rat cardiomyocytes were incubated with 33.3 mM of glucose to mimic the high glucose (HG) in diabetes...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28295415/adipose-tissue-nad-biology-in-obesity-and-insulin-resistance-from-mechanism-to-therapy
#10
REVIEW
Shintaro Yamaguchi, Jun Yoshino
Nicotinamide adenine dinucleotide (NAD(+) ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD(+) biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD(+) biosynthesis, together with its key downstream mediator, namely the NAD(+) -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner...
May 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28288617/the-effect-of-pomegranate-fresh-juice-versus-pomegranate-seed-powder-on-metabolic-indices-lipid-profile-inflammatory-biomarkers-and-the-histopathology-of-pancreatic-islets-of-langerhans-in-streptozotocin-nicotinamide-induced-type-2-diabetic-sprague-dawley-rats
#11
Seyedeh Zeinab Taheri Rouhi, Md Moklesur Rahman Sarker, Asmah Rahmat, Saad Ahmed Alkahtani, Fauziah Othman
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles. Several functional foods have therapeutic potential to treat chronic diseases including diabetes. The therapeutic potential of pomegranate has been stated by multitudinous scientists. The present study aimed to evaluate the effects of pomegranate juice and seed powder on the levels of plasma glucose and insulin, inflammatory biomarkers, lipid profiles, and health of the pancreatic islets of Langerhans in streptozotocin (STZ)-nicotinamide (NAD) induced T2DM Sprague Dawley (SD) rats...
March 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28285806/mitochondrial-sirtuins-and-molecular-mechanisms-of-aging
#12
REVIEW
Robert A H van de Ven, Daniel Santos, Marcia C Haigis
Advancing age is the major risk factor for the development of chronic diseases and is accompanied by changes in metabolic processes and mitochondrial dysfunction. Mitochondrial sirtuins (SIRT3-5) are part of the sirtuin family of NAD(+)-dependent deacylases and ADP-ribosyl transferases. The dependence on NAD(+) links sirtuin enzymatic activity to the metabolic state of the cell, poising them as stress sensors. Recent insights have revealed that SIRT3-5 orchestrate stress responses through coordinated regulation of substrate clusters rather than of a few key metabolic enzymes...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28270525/adipocyte-sirt1-controls-systemic-insulin-sensitivity-by-modulating-macrophages-in-adipose-tissue
#13
Xiaoyan Hui, Mingliang Zhang, Ping Gu, Kuai Li, Yuan Gao, Donghai Wu, Yu Wang, Aimin Xu
Adipose tissue inflammation, characterized by augmented infiltration and altered polarization of macrophages, contributes to insulin resistance and its associated metabolic diseases. The NAD(+)-dependent deacetylase SIRT1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT1 in adipocytes and myeloid cells were monitored. Compared to myeloid-specific SIRT1 depletion, mice with adipocyte-selective deletion of SIRT1 are more susceptible to diet-induced insulin resistance...
April 2017: EMBO Reports
https://www.readbyqxmd.com/read/28253885/the-nuclear-factor-erythroid-derived-2-like-2-nrf2-activator-dh404-protects-against-diabetes-induced-endothelial-dysfunction
#14
Arpeeta Sharma, Luddwi Rizky, Nada Stefanovic, Mitchel Tate, Rebecca H Ritchie, Keith W Ward, Judy B de Haan
BACKGROUND: Vascular dysfunction is a pivotal event in the development of diabetes-associated vascular disease. Increased inflammation and oxidative stress are major contributors to vascular dysfunction. Nrf2, a master regulator of several anti-oxidant genes and a suppressor of inflammatory NF-κB, has potential as a target to combat oxidative stress and inflammation. The aim of this study was to investigate the effects of a novel Nrf2 activator, the bardoxolone methyl derivative dh404, on endothelial function in vitro and in vivo...
March 3, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28250020/fat-specific-sirt6-ablation-sensitizes-mice-to-high-fat-diet-induced-obesity-and-insulin-resistance-by-inhibiting-lipolysis
#15
Jiangying Kuang, Yuwei Zhang, Qinhui Liu, Jing Shen, Shiyun Pu, Shihai Cheng, Lei Chen, Hong Li, Tong Wu, Rui Li, Yanping Li, Min Zou, Zhiyong Zhang, Wei Jiang, Guoheng Xu, Aijuan Qu, Wen Xie, Jinhan He
Sirt6 is an NAD(+)-dependent deacetylase that is involved in the control of energy metabolism. However, the tissue-specific function of Sirt6 in the adipose tissue remains unknown. Here we showed that fat-specific Sirt6 knockout (FKO) sensitized mice to high-fat diet (HFD)-induced obesity, which was attributed to adipocyte hypertrophy rather than adipocyte hyperplasia. The adipocyte hypertrophy in FKO mice likely resulted from compromised lipolytic activity as an outcome of decreased expression of adipose triglyceride lipase (ATGL), a key lipolytic enzyme...
March 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#16
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28178612/dietary-soy-protein-improves-adipose-tissue-dysfunction-by-modulating-parameters-related-with-oxidative-stress-in-dyslipidemic-insulin-resistant-rats
#17
Paola G Illesca, Silvina M Álvarez, Dante A Selenscig, María Del R Ferreira, María S Giménez, Yolanda B Lombardo, María E D'Alessandro
The present study investigates the benefits of the dietary intake of soy protein on adipose tissue dysfunction in a rat model that mimics several aspects of the human metabolic syndrome. Wistar rats were fed a sucrose-rich diet (SRD) for 4 months. After that, half of the animals continued with SRD until month 8 while in the other half, casein protein was replaced by isolated soy protein for 4 months (SRD-S). A reference group consumed a control diet all the time. In adipose tissue we determined: i) the activities of antioxidant enzymes, gene expression of Mn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glutathione redox state ii) the activity of xanthine oxidase (XO), ROS levels and the gene expression of NAD(P)H oxidase iii) the expression of the nuclear factor erythroid-2 related factor-2 (Nrf2)...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28122227/protection-against-high-fat-diet-induced-obesity-in-mdm2-c305f-mice-due-to-reduced-p53-activity-and-enhanced-energy-expenditure
#18
Shijie Liu, Tae-Hyung Kim, Derek A Franklin, Yanping Zhang
The RPL11-MDM2 interaction constitutes a p53 signaling pathway activated by deregulated ribosomal biosynthesis in response to stress. Mice bearing an MDM2(C305F) mutation that disrupts RPL11-MDM2 binding were analyzed on a high-fat diet (HFD). The Mdm2(C305F/C305F) mice, although phenotypically indistinguishable from wild-type (WT) mice when fed normal chow, demonstrated decreased fat accumulation along with improved insulin sensitivity and glucose tolerance after prolonged HFD feeding. We found that HFD increases expression of c-MYC and RPL11 in both WT and Mdm2(C305F/C305F) mice; however, p53 was induced in WT but not in Mdm2(C305F/C305F) mice...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28068222/long-term-administration-of-nicotinamide-mononucleotide-mitigates-age-associated-physiological-decline-in-mice
#19
Kathryn F Mills, Shohei Yoshida, Liana R Stein, Alessia Grozio, Shunsuke Kubota, Yo Sasaki, Philip Redpath, Marie E Migaud, Rajendra S Apte, Koji Uchida, Jun Yoshino, Shin-Ichiro Imai
NAD(+) availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD(+) intermediate, has been shown to enhance NAD(+) biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12-month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD(+) in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28003588/effectiveness-of-medium-chain-triglyceride-oil-therapy-in-two-japanese-citrin-deficient-siblings-evaluation-using-oral-glucose-tolerance-tests
#20
Hiroki Otsuka, Hideo Sasai, Elsayed Abdelkreem, Norio Kawamoto, Minako Kawamoto, Toshiya Kamiya, Yasuo Tanimoto, Atsuo Kikuchi, Shigeo Kure, Chikahiko Numakura, Kiyoshi Hayasaka, Toshiyuki Fukao
Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD(+) ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis...
2016: Tohoku Journal of Experimental Medicine
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