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Glucose metabolism and autophagy

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https://www.readbyqxmd.com/read/29145032/intravenous-immunoglobulin-improves-glucose-control-and-%C3%AE-cell-function-in-human-iapp-transgenic-mice-by-attenuating-islet-inflammation-and-reducing-iapp-oligomers
#1
Yue Zhang, Xiao-Lin Yu, Jie Zhu, Shu-Ying Liu, Xiang-Meng Liu, Quan-Xiu Dong, Jia-Qian Chai, Rui-Tian Liu
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by β-cell loss, insulin resistance, islet inflammation and amyloid deposits derived from islet amyloid polypeptide (IAPP). Reducing toxic IAPP oligomers and inhibiting islet inflammation may provide therapeutic benefit in treating T2DM. Intravenous immunoglobulin (IVIg) is an efficient anti-inflammatory and immunomodulatory agent for the treatment of several autoimmune or inflammatory neurological diseases. However, whether IVIg has therapeutic potential on T2DM remains unclear...
November 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29137236/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#2
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109032/molecular-mechanisms-of-cardiac-pathology-in-diabetes-experimental-insights
#3
REVIEW
U Varma, P Koutsifeli, V L Benson, K M Mellor, L M D Delbridge
Diabetic cardiomyopathy is a distinct pathology independent of co-morbidities such as coronary artery disease and hypertension. Diminished glucose uptake due to impaired insulin signaling and decreased expression of glucose transporters is associated with a shift towards increased reliance on fatty acid oxidation and reduced cardiac efficiency in diabetic hearts. The cardiac metabolic profile in diabetes is influenced by disturbances in circulating glucose, insulin and fatty acids, and alterations in cardiomyocyte signaling...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29107505/system-wide-benefits-of-intermeal-fasting-by-autophagy
#4
Nuria Martinez-Lopez, Elena Tarabra, Miriam Toledo, Marina Garcia-Macia, Srabani Sahu, Luisa Coletto, Ana Batista-Gonzalez, Nir Barzilai, Jeffrey E Pessin, Gary J Schwartz, Sander Kersten, Rajat Singh
Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin...
October 24, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29107216/pharmacological-effects-and-potential-therapeutic-targets-of-dt-13
#5
REVIEW
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29104532/specific-physical-exercise-improves-energetic-metabolism-in-the-skeletal-muscle-of-amyotrophic-lateral-sclerosis-mice
#6
Céline Desseille, Séverine Deforges, Olivier Biondi, Léo Houdebine, Domenico D'amico, Antonin Lamazière, Cédric Caradeuc, Gildas Bertho, Gaëlle Bruneteau, Laure Weill, Jean Bastin, Fatima Djouadi, François Salachas, Philippe Lopes, Christophe Chanoine, Charbel Massaad, Frédéric Charbonnier
Amyotrophic Lateral Sclerosis is an adult-onset neurodegenerative disease characterized by the specific loss of motor neurons, leading to muscle paralysis and death. Although the cellular mechanisms underlying amyotrophic lateral sclerosis (ALS)-induced toxicity for motor neurons remain poorly understood, growing evidence suggest a defective energetic metabolism in skeletal muscles participating in ALS-induced motor neuron death ultimately destabilizing neuromuscular junctions. In the present study, we report that a specific exercise paradigm, based on a high intensity and amplitude swimming exercise, significantly improves glucose metabolism in ALS mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29103907/myeloid-atg16l1-does-not-affect-adipose-tissue-inflammation-or-body-mass-in-mice-fed-high-fat-diet
#7
Evelyn M S Litwinoff, Merav Y Gold, Karan Singh, Jiyuan Hu, Huilin Li, Ken Cadwell, Ann Marie Schmidt
BACKGROUND: An influx of lipid-loaded macrophages characterizes visceral adipose tissue (VAT) inflammation, which is an important factor in the development of insulin resistance (IR) in obesity. Depletion of macrophage lipids accompanies increased whole body insulin sensitivity, but the underlying mechanism is unknown. Deficiency of autophagy protein ATG16L1 is associated with increases in inflammatory diseases and lipid metabolism, but the connection between ATG16L1, IR, and obesity remains elusive...
November 2, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/29094484/degradation-of-ampk-%C3%AE-1-sensitizes-braf-inhibitor-resistant-melanoma-cells-to-arginine-deprivation
#8
Ying-Ying Li, Chunjing Wu, Sumedh S Shah, Shu-Mei Chen, Medhi Wangpaichitr, Macus T Kuo, Lynn G Feun, Xiaoqing Han, Miguel Suarez, Jeffrey Prince, Niramol Savaraj
Melanomas harboring BRAF mutation (V600E) are known to recur frequently following treatment with BRAF inhibitors (BRAFi) despite a high initial response rate. Our previous study has uncovered that BRAFi-resistant melanoma (BR) cells are vulnerable to arginine deprivation. It has been reported that naïve melanoma cells undergo autophagy and re-express argininosuccinate synthetase 1 (ASS1) to enable them to synthesize arginine for survival when encountering arginine deprivation. Abolishing these two factors in BR cells confers sensitivity to arginine deprivation...
November 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29079776/sulfur-availability-regulates-plant-growth-via-glucose-tor-signaling
#9
Yihan Dong, Marleen Silbermann, Anna Speiser, Ilaria Forieri, Eric Linster, Gernot Poschet, Arman Allboje Samami, Mutsumi Wanatabe, Carsten Sticht, Aurelio A Teleman, Jean-Marc Deragon, Kazuki Saito, Rüdiger Hell, Markus Wirtz
Growth of eukaryotic cells is regulated by the target of rapamycin (TOR). The strongest activator of TOR in metazoa is amino acid availability. The established transducers of amino acid sensing to TOR in metazoa are absent in plants. Hence, a fundamental question is how amino acid sensing is achieved in photo-autotrophic organisms. Here we demonstrate that the plant Arabidopsis does not sense the sulfur-containing amino acid cysteine itself, but its biosynthetic precursors. We identify the kinase GCN2 as a sensor of the carbon/nitrogen precursor availability, whereas limitation of the sulfur precursor is transduced to TOR by downregulation of glucose metabolism...
October 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29074621/the-trpc1-ca-2-permeable-channel-inhibits-exercise-induced-protection-against-high-fat-diet-induced-obesity-and-type-ii-diabetes
#10
Danielle Krout, Anne Schaar, Yuyang Sun, Pramod Sukumaran, James N Roemmich, Brij B Singh, Kate J Claycombe-Larson
The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+ permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of cellular energy metabolism resulting in insulin resistance thereby leading to diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1 is involved in exercise-induced insulin sensitivity. The role of TRPC1 in adiposity and obesity-associated metabolic diseases has not yet been determined...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29074597/s-nitrosoglutathione-reductase-dysfunction-contributes-to-obesity-associated-hepatic-insulin-resistance-via-regulating-autophagy
#11
Qingwen Qian, Zeyuan Zhang, Allyson Orwig, Songhai Chen, Wen-Xing Ding, Yanji Xu, Ryan C Kunz, Nicholas R L Lind, Jonathan S Stamler, Ling Yang
Obesity is associated with elevated intracellular nitric oxide (NO) production, which promotes nitrosative stress in metabolic tissues such as liver and skeletal muscle, contributing to insulin resistance. The onset of obesity-associated insulin resistance is due, in part, to the compromise of hepatic autophagy, a process that leads to lysosomal degradation of cellular components. However, it is not known how NO bioactivity might impact autophagy in obesity. Here, we establish that S-nitrosoglutathione reductase (GSNOR), a major protein denitrosylase, provides a key regulatory link between inflammation and autophagy, which is disrupted in obesity and diabetes...
October 26, 2017: Diabetes
https://www.readbyqxmd.com/read/29049853/nutrient-driven-o-glcnac-in-proteostasis-and-neurodegeneration
#12
REVIEW
Ilhan Akan, Stephanie Olivier-Van Stichelen, Michelle R Bond, John A Hanover
Proteostasis is essential in the mammalian brain where post-mitotic cells must function for decades to maintain synaptic contacts and memory. The brain is dependent on glucose and other metabolites for proper function and is spared from metabolic deficits even during starvation. In this review, we outline how the nutrient sensitive nucleocytoplasmic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) regulates protein homeostasis. The O-GlcNAc modification is highly abundant in the mammalian brain, and has been linked to proteopathies, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29042435/autophagy-induction-under-carbon-starvation-conditions-is-negatively-regulated-by-carbon-catabolite-repression
#13
Atsuhiro Adachi, Michiko Koizumi, Yoshinori Ohsumi
Autophagy is a conserved process in which cytoplasmic components are sequestered for degradation in the vacuole/lysosomes in eukaryotic cells. Autophagy is induced under a variety of starvation conditions, such as the depletion of nitrogen, carbon, phosphorus, zinc and others. However, apart from nitrogen starvation, it remains unclear how these stimuli induce autophagy. In yeast, for example, it remains contentious whether autophagy is induced under carbon starvation conditions, with reports variously suggesting both induction and lack of induction upon depletion of carbon...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29039446/protective-effect-of-autophagy-in-neural-ischemia-and-hypoxia-negative-regulation-of-the-wnt-%C3%AE-catenin-pathway
#14
Zhen-Yu Shi, Jie-Xin Deng, Su Fu, Lai Wang, Qiang Wang, Bin Liu, Yong-Qiang Li, Jin-Bo Deng
Autophagy is a highly conserved process of self-digestion to promote cell survival in response to nutrient starvation and other metabolic stresses. However, whether ischemic-hypoxic (IH) injury-induced autophagy acts as a neuroprotective mechanism or leads to neuroinjury is a subject of debate. It is known that autophagy is regulated by signaling pathways, including the mammalian target of rapamycin pathway. However, in neural IH injury, whether other signaling pathways are involved in the regulation of autophagy remains to be fully elucidated...
September 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29024899/mangiferin-ameliorates-fatty-liver-via-modulation-of-autophagy-and-inflammation-in-high-fat-diet-induced-mice
#15
Hu Wang, Yang-Yang Zhu, Li Wang, Tian Teng, Meng Zhou, Shu-Guang Wang, Yi-Zhu Tian, Lei Du, Xiao-Xing Yin, Ying Sun
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The progression of NAFLD is complex and associated with inflammation, oxidative stress, autophagy, endoplasmic reticulum stress, and insulin resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show multiple biological activities. The aim of this study was to investigate the therapeutic effect of mangiferin on NAFLD and the underlying molecular mechanism. We established a mouse model of NAFLD using a high-fat diet (HFD), and injected the mice with different doses of mangiferin (15, 30, and 60mg/kg, intraperitoneal) for 12 weeks...
October 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29017418/maternal-glucose-supplementation-in-a-murine-model-of-chorioamnionitis-alleviates-dysregulation-of-autophagy-in-fetal-brain
#16
Jun Lei, Wenyu Zhong, Ahmad Almalki, Hongxi Zhao, Hattan Arif, Rayyan Rozzah, Ghada Al Yousif, Nader Alhejaily, Dan Wu, Michael McLane, Irina Burd
Fetal brain injury induced by intrauterine inflammation is a major risk factor for adverse neurological outcomes, including cerebral palsy, cognitive dysfunction, and behavioral disabilities. There are no adequate therapies for neuronal protection to reduce fetal brain injury, especially new strategies that may apply promptly and conveniently. In this study, we explored the effect of maternal glucose administration in a mouse model of intrauterine inflammation at term. Our results demonstrated that maternal glucose supplementation significantly increased survival birth rate and improved the neurobehavioral performance of pups exposed to intrauterine inflammation...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28986309/farnesoid-x-receptor-a-homeostat-for-hepatic-nutrient-metabolism
#17
REVIEW
Vittoria Massafra, Saskia W C van Mil
The Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids (BAs). BAs are amphipathic molecules that serve as fat solubilizers in the intestine under postprandial conditions. In the post-absorptive state, BAs bind FXR in the hepatocytes, which in turn provides feedback signals on BA synthesis and transport and regulates lipid, glucose and amino acid metabolism. Therefore, FXR acts as a homeostat of all three classes of nutrients, fats, sugars and proteins. Here we re-analyze the function of FXR in the perspective of nutritional metabolism, and discuss the role of FXR in liver energy homeostasis in postprandial, post-absorptive and fasting/starvation states...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28980855/regulation-of-glycolytic-metabolism-by-autophagy-in-liver-cancer-involves-selective-autophagic-degradation-of-hk2-hexokinase-2
#18
Lin Jiao, Hai-Liang Zhang, Dan-Dan Li, Ke-Li Yang, Jun Tang, Xuan Li, Jiao Ji, Yan Yu, Rui-Yan Wu, Senthilkumar Ravichandran, Jian-Jun Liu, Gong-Kan Feng, Min-Shan Chen, Yi-Xin Zeng, Rong Deng, Xiao-Feng Zhu
Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level. The autophagic degradation of HK2 (hexokinase 2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate, was found to be involved in the regulation of glycolysis by autophagy...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28977989/the-molecular-basis-of-targeting-pfkfb3-as-a-therapeutic-strategy-against-cancer
#19
Luo Lu, Yaoyu Chen, Yu Zhu
6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases (PFKFBs) are bifunctional enzymes which regulate the transformation between fructose-2, 6-bisphosphate (F2, 6BP) and fructose-6-phosphate (F6P) in the process of glucose metabolism. Among the four isozymes (PFKFB1-4), PFKFB3 has stronger kinase activity than phosphatase activity, resulting in the synthesis of F2, 6BP and the promotion of glycolysis. Additionally, PFKFB3 plays a key role in cell cycle regulation. It has been confirmed that PFKFB3 is upregulated in a variety of tumor cells, and inhibition of it results in suppression of the growth of tumor cells by downregulating the glycolytic flux...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974774/ampk-guardian-of-metabolism-and-mitochondrial-homeostasis
#20
REVIEW
Sébastien Herzig, Reuben J Shaw
Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism...
October 4, 2017: Nature Reviews. Molecular Cell Biology
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