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Glucose metabolism and autophagy

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https://www.readbyqxmd.com/read/29285270/metformin-alleviates-nickel-induced-autophagy-and-apoptosis-via-inhibition-of-hexokinase-2-activating-lipocalin-2-in-human-bronchial-epithelial-cells
#1
Yu-Ting Kang, Wen-Cheng Hsu, Chih-Hsien Wu, I-Lun Hsin, Pei-Ru Wu, Kun-Tu Yeh, Jiunn-Liang Ko
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273519/adenosine-monophosphate-activated-protein-kinase-modulation-by-berberine-attenuates-mitochondrial-deficits-and-redox-imbalance-in-experimental-diabetic-neuropathy
#2
Veera Ganesh Yerra, Anil Kumar Kalvala, Bhoomika Sherkhane, Aparna Areti, Ashutosh Kumar
Adenosine monophosphate activated protein kinase (AMPK) has been studied for its myriad metabolic and mitochondrial benefits in several chronic diseases. Recent studies have uncovered its therapeutic potential against mitochondrial dysfunction in cultured dorsal root ganglion (DRG) neurons isolated from streptozotocin (STZ) induced diabetic rats. The present study is aimed at evaluating the pharmacological efficacy of berberine (BRB), a natural AMPK activator against experimental diabetic neuropathy (DN) phenotype developed in STZ (55 mg/kg, i...
December 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29273412/versatility-of-microglial-bioenergetic-machinery-under-starving-conditions
#3
Adam M Nagy, Rebeka Fekete, Gergo Horvath, Gabor Koncsos, Csilla Kriston, Anna Sebestyen, Zoltan Giricz, Zsuzsanna Kornyei, Emilia Madarasz, Laszlo Tretter
Microglia are highly dynamic cells in the brain. Their functional diversity and phenotypic versatility brought microglial energy metabolism into the focus of research. Although it is known that microenvironmental cues shape microglial phenotype, their bioenergetic response to local nutrient availability remains unclear. In the present study effects of energy substrates on the oxidative and glycolytic metabolism of primary - and BV-2 microglial cells were investigated. Cellular oxygen consumption, glycolytic activity, the levels of intracellular ATP/ADP, autophagy, mTOR phosphorylation, apoptosis and cell viability were measured in the absence of nutrients or in the presence of physiological energy substrates: glutamine, glucose, lactate, pyruvate or ketone bodies...
December 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29246323/triptolide-restores-autophagy-to-alleviate-diabetic-renal-fibrosis-through-the-mir-141-3p-pten-akt-mtor-pathway
#4
Xiao-Yu Li, Shan-Shan Wang, Zhe Han, Fei Han, Yun-Peng Chang, Yang Yang, Mei Xue, Bei Sun, Li-Ming Chen
Fibrosis is the major pathological feature of diabetic kidney disease (DKD). Autophagy, a process to maintain metabolic homeostasis, is obviously inhibited in DKD. Triptolide (TP) is a traditional Chinese medicine extract known for immune suppression and anti-inflammatory and anti-cancer activities. In this study, we investigated the effects of TP on autophagy and fibrosis in DKD. TP restored autophagy and alleviated fibrosis in DKD rats and high-glucose-incubated human mesangial cells. After we applied 3-methyladenine (an autophagy inhibitor) and autophagy-related gene 5-small interfering RNA (siRNA), we found that the improvement of fibrosis on TP was related to the restoration of autophagy...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29234478/fructose-ingestion-impairs-expression-of-genes-involved-in-skeletal-muscle-s-adaptive-response-to-aerobic-exercise
#5
Natalia Gomes Gonçalves, Stephanie Heffer Cavaletti, Carlos Augusto Pasqualucci, Milton Arruda Martins, Chin Jia Lin
Background: The inverse relationship between exercise capacity and its variation over time and both cardiovascular and all-cause mortality suggests the existence of an etiological nexus between cardiometabolic diseases and the molecular regulators of exercise capacity. Coordinated adaptive responses elicited by physical training enhance exercise performance and metabolic efficiency and possibly mediate the health benefits of physical exercise. In contrast, impaired expression of genes involved in mitochondrial biogenesis or protein turnover in skeletal muscle-key biological processes involved in adaptation to physical training-leads to insulin resistance and obesity...
2017: Genes & Nutrition
https://www.readbyqxmd.com/read/29224880/the-effect-of-different-treatments-for-early-lactation-hyperketonemia-on-liver-triglycerides-glycogen-and-expression-of-key-metabolic-enzymes-in-dairy-cattle
#6
S Mann, F A Leal Yepes, J J Wakshlag, E Behling-Kelly, J A A McArt
Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism...
December 7, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29205673/mechanisms-of-ampk-in-the-maintenance-of-atp-balance-during-energy-metabolism
#7
REVIEW
Rong Ke, Qicao Xu, Cong Li, Lingyu Luo, Deqiang Huang
AMP-activated protein kinase (AMPK) is a conserved sensor of cellular energy change and is activated by increased AMP/ATP and/or ADP/ATP ratios. AMPK maintains the energy balance by decreasing the ATP-consuming processes such as transcription of synthetic fat genes and rRNA, the translation of ribosomal proteins, synthesis of cholesterol and fatty acid, while the metabolic pathways such as glucose and fatty transport, fatty acid oxidation, autophagy, mitochondrial synthesis and oxidative metabolism are increased to preserve ATP during energy deficiency...
December 4, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29203581/cardiac-insulin-signaling-regulates-glycolysis-through-phosphofructokinase-2-content-and-activity
#8
Lee B Bockus, Satoshi Matsuzaki, Shraddha S Vadvalkar, Zachary T Young, Jennifer R Giorgione, Maria F Newhardt, Michael Kinter, Kenneth M Humphries
BACKGROUND: The healthy heart has a dynamic capacity to respond and adapt to changes in nutrient availability. Diabetes mellitus disrupts this metabolic flexibility and promotes cardiomyopathy through mechanisms that are not completely understood. Phosphofructokinase 2 (PFK-2) is a primary regulator of cardiac glycolysis and substrate selection, yet its regulation under normal and pathological conditions is unknown. This study was undertaken to determine how changes in insulin signaling affect PFK-2 content, activity, and cardiac metabolism...
December 4, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29180704/vps34-pi-3-kinase-inactivation-enhances-insulin-sensitivity-through-reprogramming-of-mitochondrial-metabolism
#9
Benoit Bilanges, Samira Alliouachene, Wayne Pearce, Daniele Morelli, Gyorgy Szabadkai, Yuen-Li Chung, Gaëtan Chicanne, Colin Valet, Julia M Hill, Peter J Voshol, Lucy Collinson, Christopher Peddie, Khaled Ali, Essam Ghazaly, Vinothini Rajeeve, Georgios Trichas, Shankar Srinivas, Claire Chaussade, Rachel S Salamon, Jonathan M Backer, Cheryl L Scudamore, Maria A Whitehead, Erin P Keaney, Leon O Murphy, Robert K Semple, Bernard Payrastre, Sharon A Tooze, Bart Vanhaesebroeck
Vps34 PI3K is thought to be the main producer of phosphatidylinositol-3-monophosphate, a lipid that controls intracellular vesicular trafficking. The organismal impact of systemic inhibition of Vps34 kinase activity is not completely understood. Here we show that heterozygous Vps34 kinase-dead mice are healthy and display a robustly enhanced insulin sensitivity and glucose tolerance, phenotypes mimicked by a selective Vps34 inhibitor in wild-type mice. The underlying mechanism of insulin sensitization is multifactorial and not through the canonical insulin/Akt pathway...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29165041/akt-mediated-phosphorylation-of-atg4b-impairs-mitochondrial-activity-and-enhances-the-warburg-effect-in-hepatocellular-carcinoma-cells
#10
Zhenhong Ni, Jintao He, Yaran Wu, Changjiang Hu, Xufang Dai, Xiaojing Yan, Bo Li, Xinzhe Li, Haojun Xiong, Yuming Li, Song Li, Liang Xu, Yongsheng Li, Jiqin Lian, Fengtian He
Phosphorylation is a major type of post-translational modification, which can influence the cellular physiological function. ATG4B, a key macroautophagy/autophagy-related protein, has a potential effect on the survival of tumor cells. However, it is still unknown as to the role of ATG4B phosphorylation in cancers. In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells. The phosphorylation of ATG4B at Ser34 had little effect on autophagic flux, but promoted the Warburg effect including the increase of L-lactate production and glucose consumption, and the decrease of oxygen consumption in HCC cells...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29158051/the-regulation-of-foxo1-and-its-role-in-disease-progression
#11
REVIEW
Ya-Qi Xing, Ang Li, Yang Yang, Xiao-Xia Li, Li-Nan Zhang, Hui-Cai Guo
Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic dysregulation are the basis of many diseases. Forkhead box transcription factor O1 (FOXO1) changes in response to cellular stimulation and maintains tissue homeostasis during the above-mentioned physiological and pathological processes. Substantial evidences indicate that FOXO1's function depends on the modulation of downstream targets such as apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29151965/combined-inhibitions-of-glycolysis-and-akt-autophagy-can-overcome-resistance-to-egfr-targeted-therapy-of-lung-cancer
#12
Mingtong Ye, Sufan Wang, Ting Wan, Rui Jiang, Yun Qiu, Lei Pei, Nengzhi Pang, Yuanling Huang, Yufeng Huang, Zhenfeng Zhang, Lili Yang
Efficacy of EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, to treat human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR is not persistent due to drug resistance. Reprogramming in energy (especially glucose) metabolism plays an important role in development and progression of acquired resistance in cancer cells. We hypothesize that glucose metabolism in EGFR-TKI sensitive HCC827 cells and erlotinib-resistant sub-line of HCC827 (which we name it as erlotinib-resistant 6, ER6 cells in this study) is different and targeting glucose metabolism might be a treatment strategy for erlotinib-resistant NSCLCs...
2017: Journal of Cancer
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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