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Glucose metabolism and autophagy

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https://www.readbyqxmd.com/read/28426655/glycosome-biogenesis-in-trypanosomes-and-the-de-novo-dilemma
#1
REVIEW
Sarah Bauer, Meredith T Morris
Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28415728/lipid-degradation-promotes-prostate-cancer-cell-survival
#2
Harri M Itkonen, Michael Brown, Alfonso Urbanucci, Gregory Tredwell, Chung Ho Lau, Stefan Barfeld, Claire Hart, Ingrid J Guldvik, Mandeep Takhar, Hannelore V Heemers, Nicholas Erho, Katarzyna Bloch, Elai Davicioni, Rita Derua, Etienne Waelkens, James L Mohler, Noel Clarke, Johan V Swinnen, Hector C Keun, Ole P Rekvig, Ian G Mills
Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28378930/hepatic-fxr-shp-axis-modulates-systemic-glucose-and-fatty-acid-homeostasis-in-aged-mice
#3
Kang Ho Kim, Sungwoo Choi, Ying Zhou, Eun Young Kim, Jae Man Lee, Pradip K Saha, Sayeepriyadarshini Anakk, David D Moore
The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global disruption of both FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages. Here, we report an unexpected beneficial impact on glucose and fatty acid metabolism in aged DKO mice, which show suppressed body weight gain and adiposity when maintained on normal chow. This phenotype was not observed in single Fxr or Shp knockouts. Liver-specific Fxr/Shp double knockout (FS(LK) °) mice fully phenocopied the DKO mice, with lower hepatic triglyceride accumulation, improved glucose/insulin tolerance and accelerated fatty acid utilization...
April 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28368722/tumor-cell-intrinsic-cd274-pd-l1-a-novel-metabolic-balancing-act-with-clinical-potential
#4
Curtis A Clark, Harshita B Gupta, Tyler J Curiel
Tumor expression of the immune co-signaling molecule CD274/PD-L1 was originally described as impeding antitumor immunity by direct engagement of its receptor, PDCD1/PD-1, on antitumor T cells. Melanoma-intrinsic PDCD1 was recently shown to promote tumor growth and MTOR signals in cooperation with tumor CD274, and sarcoma-intrinsic CD274 signaling promotes glucose metabolism to impede antitumor immunity. Our recent report shows that tumor cell-intrinsic CD274 promotes MTORC1 signaling in mouse melanoma and mouse and human ovarian cancer, inhibits autophagy and sensitizes some tumors to clinically available pharmacological autophagy inhibitors and confers resistance to MTOR inhibitors...
April 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28367063/understanding-the-role-of-pd-l1-pd1-pathway-blockade-and-autophagy-in-cancer-therapy
#5
REVIEW
Marianela Robainas, Rafael Otano, Stephen Bueno, Sihem Ait-Oudhia
Autophagy is a vital, physiological catabolic process for cell survival by which cells clear damaged organelles and recycle nutrients when homeostasis is maintained. Cancer is a complex disease with uncontrolled growth of cancer cells. Recent studies have suggested the role of autophagy in cancer. A complex relationship exists between autophagy and cancer, since autophagy can contribute to the survival or the destruction of malignant cells depending on the stage of tumor development. In this review, we describe in detail the mechanism underlying autophagy in cancer cells and the intricate involvement of the programmed cell death-1 (PD1) receptor with its ligand (PD-L1)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28356082/anti-tumor-effects-of-everolimus-and-metformin-are-complementary-and-glucose-dependent-in-breast-cancer-cells
#6
Gerke Ariaans, Mathilde Jalving, Emma Geertruida Elisabeth de Vries, Steven de Jong
BACKGROUND: Clinical efficacy of the mTOR inhibitor everolimus is limited in breast cancer and regularly leads to side-effects including hyperglycemia. The AMPK inhibitor and anti-diabetic drug metformin may counteract everolimus-induced hyperglycemia, as well as enhancing anti-cancer efficacy. We investigated the glucose-dependent growth-inhibitory properties of everolimus, metformin and the combination in breast cancer cell lines. METHODS: The breast cancer cell lines MCF-7, MDA-MB-231 and T47D were cultured in media containing 11 mM or 2...
March 29, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28353649/high-dietary-fructose-direct-or-indirect-dangerous-factors-disturbing-tissue-and-organ-functions
#7
REVIEW
Dong-Mei Zhang, Rui-Qing Jiao, Ling-Dong Kong
High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors...
March 29, 2017: Nutrients
https://www.readbyqxmd.com/read/28351381/the-role-of-stromal-cancer-associated-fibroblasts-in-pancreatic-cancer
#8
REVIEW
Dagny von Ahrens, Tushar D Bhagat, Deepak Nagrath, Anirban Maitra, Amit Verma
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6...
March 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28342290/verapamil-treatment-induces-cytoprotective-autophagy-by-modulating-cellular-metabolism
#9
Elżbieta Kania, Beata Pająk, 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 (CQ) 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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%...
April 2017: Obesity
https://www.readbyqxmd.com/read/28237097/magnetic-resonance-spectroscopy-to-study-glycolytic-metabolism-during-autophagy
#16
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
#17
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
#18
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
#19
REVIEW
Sojin Lee, H Henry 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...
May 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
#20
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-)
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