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Glucose metabolism and autophagy

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https://www.readbyqxmd.com/read/28342290/verapamil-treatment-induces-cytoprotective-autophagy-by-modulating-cellular-metabolism
#1
Elzbieta Kania, Beata Pajak, Jim O'Prey, Pablo Sierra Gonzalez, Anna Litwiniuk, Kaja Urbańska, Kevin M Ryan, Arkadiusz Orzechowski
Verapamil, an L-type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with Verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of Verapamil on autophagy and cell viability in greater detail. We report here that Verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine or by CRISPR/Cas9-mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to Verapamil...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28336389/metformin-ameliorates-uterine-defects-in-a-rat-model-of-polycystic-ovary-syndrome
#2
Yuehui Zhang, Min Hu, Fanci Meng, Xiaoyan Sun, Hongfei Xu, Jiao Zhang, Peng Cui, Njomeza Morina, Xin Li, Wei Li, Xiao-Ke Wu, Mats Brännström, Ruijin Shao, Håkan Billig
Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus...
March 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28320861/recycling-of-iron-via-autophagy-is-critical-for-the-transition-from-glycolytic-to-respiratory-growth
#3
Tetsuro Horie, Tomoko Kawamata, Miou Matsunami, Yoshinori Ohsumi
Autophagy is a bulk degradation process conserved from yeast to mammals. To examine the roles of autophagy in cellular metabolism, we generated autophagy-defective (atg) mutants in the X2180-1B strain background. We compared the growth of wild type (WT) and atg cells in minimal (synthetic dextrose, SD) and rich (yeast extract-peptone-dextrose, YEPD) medium, and found that mutations in the core autophagy machinery results in defects in the diauxic shift, the transition from fermentation to respiratory growth upon glucose depletion, specifically in SD...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301876/autophagy-inhibitor-chloroquine-increases-sensitivity-to-cisplatin-in-qbc939-cholangiocarcinoma-cells-by-mitochondrial-ros
#4
Xianzhi Qu, Jiyao Sheng, Luyan Shen, Jing Su, Yunjie Xu, Qi Xie, Yao Wu, Xuewen Zhang, Liankun Sun
The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28300563/sestrin-2-induces-autophagy-and-attenuates-insulin-resistance-by-regulating-ampk-signaling-in-c2c12-myotubes
#5
Huige Li, Sujuan Liu, Hairui Yuan, Yanmei Niu, Li Fu
Impaired insulin-stimulated glucose uptake in skeletal muscle serves a critical role in the development of insulin resistance (IR), whereas the precise mechanism of the process remains unknown. Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes. Activation of Sesn2 may activate AMP-activated protein kinase (AMPK) accompanied by suppression of mammalian target of rapamycin (mTOR), which may ultimately lead to autophagy induction...
March 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28277987/endoc-%C3%AE-h1-cells-display-increased-sensitivity-to-sodium-palmitate-when-cultured-in-dmem-f12-medium
#6
Camilla Krizhanovskii, Hjalti Kristinsson, Andris Elksnis, Xuan Wang, Hamid Gavali, Peter Bergsten, Raphael Scharfmann, Nils Welsh
Aims - Human pancreatic islets are known to die in response to the free fatty acid of sodium palmitate when cultured in vitro. This is in contrast to EndoC-βH1 cells, which in our hands are not sensitive to the cell death-inducing effects sodium palmitate, making these cells seemingly unsuitable for lipotoxicity studies. However, the EndoC-βH1 cells are routinely cultured in a nutrient mixture based on Dulbecco's Modified Eagle Medium (DMEM), which may not be the optimal choice for studies dealing with lipotoxicity...
February 28, 2017: Islets
https://www.readbyqxmd.com/read/28245099/hiv-infection-does-not-prevent-the-metabolic-benefits-of-diet-induced-weight-loss-in-women-with-obesity
#7
Dominic N Reeds, Terri A Pietka, Kevin E Yarasheski, W Todd Cade, Bruce W Patterson, Adewole Okunade, Nada A Abumrad, Samuel Klein
OBJECTIVE: To test the hypothesis that HIV infection impairs the beneficial effects of weight loss on insulin sensitivity, adipose tissue inflammation, and endoplasmic reticulum (ER) stress. METHODS: A prospective clinical trial evaluated the effects of moderate diet-induced weight loss on body composition, metabolic function, and adipose tissue biology in women with obesity who were HIV-seronegative (HIV-) or HIV-positive (HIV+). Body composition, multiorgan insulin sensitivity (assessed by using a two-stage hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions), and adipose tissue expression of markers of inflammation, autophagy, and ER stress were evaluated in 8 HIV- and 20 HIV+ women with obesity before and after diet-induced weight loss of 6% to 8%...
February 28, 2017: Obesity
https://www.readbyqxmd.com/read/28237097/magnetic-resonance-spectroscopy-to-study-glycolytic-metabolism-during-autophagy
#8
Y-L Chung, M O Leach, T R Eykyn
Cancer cells undergoing starvation- and treatment-induced autophagy were found to exhibit reduced intracellular lactate, reduced rates of steady-state lactate excretion and reduced real-time pyruvate-lactate exchange rates, indicating that glycolytic metabolism was altered in autophagic cells. In this chapter, we describe the technical details of the use of (1)H-magnetic resonance spectroscopy (MRS) to measure endogenous cellular concentrations of lactate and glucose in autophagic cells and tissues, how to measure the rate of steady-state lactate excretion and glucose uptake by (1)H-MRS in autophagic cells, and details of the real-time measurement of [1-(13)C] pyruvate to lactate exchange in autophagic cells by (13)C-MRS-DNP (dynamic nuclear polarization)...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#9
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#10
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28213398/foxo-integration-of-insulin-signaling-with-glucose-and-lipid-metabolism
#11
Sojin Lee, Henry H Dong
The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA binding domain, known as "forkhead box" domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals...
February 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#12
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28183450/the-role-of-short-chain-fatty-acids-in-kidney-injury-induced-by-gut-derived-inflammatory-response
#13
REVIEW
Wei Huang, Luping Zhou, Hengli Guo, Youhua Xu, Yong Xu
It has been found that several circulating metabolites derived from gut microbiota fermentation associate with a systemic immuno-inflammatory response and kidney injury, which has been coined the gut-kidney axis. Recent evidence has suggested that short-chain fatty acids (SCFAs), which are primarily originated from fermentation of dietary fiber in the gut, play an important role in regulation of immunity, blood pressure, glucose and lipid metabolism, and seem to be the link between microbiota and host homeostasis...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28153729/4-pba-reverses-autophagic-dysfunction-and-improves-insulin-sensitivity-in-adipose-tissue-of-obese-mice-via-akt-mtor-signaling
#14
Qinyue Guo, Lin Xu, Huixia Li, Hongzhi Sun, Shufang Wu, Bo Zhou
BACKGROUND: 4-phenyl butyric acid (4-PBA) has been considered as a key regulator of insulin resistance in obesity. However the mechanism of 4-PBA involved in insulin resistance remains elusive. METHODS: We evaluated the effect of 4-PBA on abnormal autophagy and endoplasmic reticulum (ER) stress in obese mice. 4-PBA was administered in obese mice and adipocyte models, and metabolic parameters, autophagy markers, ER stress indicators, Akt/mTOR signaling and insulin signaling molecular were assessed...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28149534/iapp-modulates-cellular-autophagy-apoptosis-and-extracellular-matrix-metabolism-in-human-intervertebral-disc-cells
#15
Xinghuo Wu, Yu Song, Wei Liu, Kun Wang, Yong Gao, Shuai Li, Zhenfeng Duan, Zengwu Shao, Shuhua Yang, Cao Yang
The pathogenic process of intervertebral disc degeneration (IDD) is characterized by imbalance in the extracellular matrix (ECM) metabolism. Nucleus pulposus (NP) cells have important roles in maintaining the proper structure and tissue homeostasis of disc ECM. These cells need adequate supply of glucose and oxygen. Islet amyloid polypeptide (IAPP) exerts its biological effects by regulating glucose metabolism. The purpose of this study was to investigate the expression of IAPP in degenerated IVD tissue, and IAPP modulation of ECM metabolism in human NP cells, especially the crosstalk mechanism between apoptosis and autophagy in these cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28143512/progranulin-causes-adipose-insulin-resistance-via-increased-autophagy-resulting-from-activated-oxidative-stress-and-endoplasmic-reticulum-stress
#16
Qinyue Guo, Lin Xu, Huixia Li, Hongzhi Sun, Jiali Liu, Shufang Wu, Bo Zhou
BACKGROUND: Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. METHODS: In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed...
January 31, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28121493/atp-driven-and-ampk-independent-autophagy-in-an-early-branching-eukaryotic-parasite
#17
Feng-Jun Li, Zhi-Shen Xu, Andy D S Soo, Zhao-Rong Lun, Cynthia Y He
Autophagy is a catabolic cellular process required to maintain protein synthesis, energy production and other essential activities in starved cells. While the exact nutrient sensor(s) is yet to be identified, deprivation of amino acids, glucose, growth factor and other nutrients can serve as metabolic stimuli to initiate autophagy in higher eukaryotes. In the early-branching unicellular parasite Trypanosoma brucei, which can proliferate as procyclic form (PCF) in the tsetse fly or as bloodstream form (BSF) in animal hosts, autophagy is robustly triggered by amino acid deficiency but not by glucose depletion...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28106298/inhibition-of-inositol-1-4-5-trisphosphate-receptor-induce-breast-cancer-cell-death-through-deregulated-autophagy-and-cellular-bioenergetics
#18
Aru Singh, Megha Chagtoo, Swasti Tiwari, Nelson George, Bandana Chakravarti, Sajid Khan, Sripada Lakshmi, Madan M Godbole
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) regulate autophagy in normal cells and are associated with metastasis in cancer cells. In breast cancer, however, the regulation and role of IP3 Rs is not clear. To study this we used MCF-7 breast cancer cell line and mouse model of breast cancer. Inhibiting IP3 R sub types resulted in compromised bioenergetics both in terms of glucose and mitochondrial metabolism. The siRNA mediated silencing of IP3 R or its blocking by its inhibitors Xestospongin C and 2-Amino-ethoxy diphenyl borate increased cell death and LC3II expression in MCF-7 cells as well as attenuated cellular bioenergetics...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28098871/lectin-pcl-inhibits-the-warburg-effect-of-pc3-cells-by-combining-with-egfr-and-inhibiting-hk2
#19
Hong Zhang, Xia Du, Ting-Ting Sun, Chun-Liu Wang, Ye Li, Shou-Zhen Wu
Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28072818/glucose-abl1-tor-signaling-modulates-cell-cycle-tuning-to-control-terminal-appressorial-cell-differentiation
#20
Margarita Marroquin-Guzman, Guangchao Sun, Richard A Wilson
The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia)...
January 2017: PLoS Genetics
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