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Glucose transporter deficiency

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https://www.readbyqxmd.com/read/27921254/the-impact-of-vitamin-d-supplementation-on-neurodegeneration-tnf-%C3%AE-concentration-in-hypothalamus-and-csf-to-plasma-ratio-of-insulin-in-high-fat-diet-induced-obese-rats
#1
Ghazaleh Nameni, Ghazaleh Hajiluian, Parviz Shahabi, Mahdieh Abbasalizad Farhangi, Mehran Mesgari-Abbasi, Mohammad-Reza Hemmati, Seyed Mahdi Vatandoust
There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27894955/blocking-preferential-glucose-uptake-sensitizes-liver-tumor-initiating-cells-to-glucose-restriction-and-sorafenib-treatment
#2
Hui-Lu Zhang, Ming-Da Wang, Xu Zhou, Chen-Jie Qin, Gong-Bo Fu, Liang Tang, Han Wu, Shuai Huang, Ling-Hao Zhao, Min Zeng, Jiao Liu, Dan Cao, Lin-Na Guo, Hong-Yang Wang, He-Xin Yan, Jie Liu
Cancer cells display altered metabolic phenotypes characterized by a high level of glycolysis, even under normoxic conditions. Because of a high rate of glycolytic flux and inadequate vascularization, tumor cells often suffer from nutrient deficiency and require metabolic adaptations to address such stresses. Although tumor-initiating cells (T-ICs) have been identified in various malignancies, the cells' metabolic phenotypes remain elusive. In this study, we observed that liver T-ICs preferentially survived under restricted glucose treatment...
November 26, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27864142/glycogen-storage-disease-type-ib-neutrophils-exhibit-impaired-cell-adhesion-and-migration
#3
Goo-Young Kim, Young Mok Lee, Joon Hyun Kwon, Hyun Sik Jun, Janice Chou
Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction, is an inherited autosomal recessive disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT). Neutrophils play an essential role in the defense against invading pathogens. The recruitment of neutrophils towards the inflammation sites in response to inflammatory stimuli is a tightly regulated process involving rolling, adhesion, and transmigration. In this study, we investigated the role of G6PT in neutrophil adhesion and migration using in vivo and in vitro models...
November 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27856334/quantitative-metabolic-flux-analysis-reveals-an-unconventional-pathway-of-fatty-acid-synthesis-in-cancer-cells-deficient-for-the-mitochondrial-citrate-transport-protein
#4
Lei Jiang, Adam Boufersaoui, Chendong Yang, Bookyung Ko, Dinesh Rakheja, Gerardo Guevara, Zeping Hu, Ralph J DeBerardinis
The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies...
November 14, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27814392/gender-specific-mechanisms-underlying-the-amelioration-of-high-fat-diet-induced-glucose-intolerance-in-b-cell-activating-factor-deficient-mice
#5
Bobae Kim, Chang-Kee Hyun
It has recently been found that B cell activating factor (BAFF) plays an important role in the regulation of energy homeostasis. We also have previously reported that BAFF deficiency reverses high-fat (HF) diet-induced glucose intolerance by potentiating adipose tissue function. In the present study, we found that BAFF deficient (BAFF-/-) mice exhibit gender-specific differences in protection against diet-induced glucose intolerance, and aimed to characterize the gender-dependent molecular alterations in energy metabolism...
2016: PloS One
https://www.readbyqxmd.com/read/27792451/lncrna-nbr2-modulates-cancer-cell-sensitivity-to-phenformin-through-glut1
#6
Xiaowen Liu, Boyi Gan
Biguanides, including metformin (widely used in diabetes treatment) and phenformin, are AMP-activated protein kinase (AMPK) activators and potential drugs for cancer treatment. A more in-depth understanding of how cancer cells adapt to biguanide treatment may provide important therapeutic implications to achieve more effective and rational cancer therapies. NBR2 is a glucose starvation-induced long non-coding RNA (lncRNA) that interacts with AMPK and regulates AMPK activity upon glucose starvation. Here we show that phenformin treatment induces NBR2 expression, and NBR2 deficiency sensitizes cancer cells to phenformin-induced cell death...
October 28, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27785828/rapid-sodium-signaling-couples-glutamate-uptake-to-breakdown-of-atp-in-perivascular-astrocyte-endfeet
#7
Julia Langer, Niklas J Gerkau, Amin Derouiche, Christian Kleinhans, Behrouz Moshrefi-Ravasdjani, Michaela Fredrich, Karl W Kafitz, Gerald Seifert, Christian Steinhäuser, Christine R Rose
Perivascular endfeet of astrocytes are highly polarized compartments that ensheath blood vessels and contribute to the blood-brain barrier. They experience calcium transients with neuronal activity, a phenomenon involved in neurovascular coupling. Endfeet also mediate the uptake of glucose from the blood, a process stimulated in active brain regions. Here, we demonstrate in mouse hippocampal tissue slices that endfeet undergo sodium signaling upon stimulation of glutamatergic synaptic activity. Glutamate-induced endfeet sodium transients were diminished by TFB-TBOA, suggesting that they were generated by sodium-dependent glutamate uptake...
October 27, 2016: Glia
https://www.readbyqxmd.com/read/27754061/os-15-09-does-ace2-angiotensin-1-7-axis-protect-from-aging-associated-loss-of-skeletal-muscle-function
#8
Hikari Takeshita, Masao Takeda, Koichi Yamamoto, Hiromi Rakugi
OBJECTIVE: Angiotensin converting enzyme2 (ACE2), an enzyme that produces the Angiotensin 1-7(A1-7) from Angiotensin II, is considered to suppress organ damage by inhibition of the activation of renin-angiotensin system. We recently found that ACE2 deficiency in mice ameliorated insulin sensitivity of skeletal muscle with reduced expression of glucose transporter 4 and myocyte enhancer factor 2, an important transcription factor to maintain homeostasis of skeletal muscle. In this study, we investigated whether ACE2-A1-7 axis plays a protective role in aging-associated loss of skeletal muscle function in mice...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27746145/enhanced-fructose-utilization-mediated-by-slc2a5-is-a-unique-metabolic-feature-of-acute-myeloid-leukemia-with-therapeutic-potential
#9
Wen-Lian Chen, Yue-Ying Wang, Aihua Zhao, Li Xia, Guoxiang Xie, Mingming Su, Linjing Zhao, Jiajian Liu, Chun Qu, Runmin Wei, Cynthia Rajani, Yan Ni, Zhen Cheng, Zhu Chen, Sai-Juan Chen, Wei Jia
Rapidly proliferating leukemic progenitor cells consume substantial glucose, which may lead to glucose insufficiency in bone marrow. We show that acute myeloid leukemia (AML) cells are prone to fructose utilization with an upregulated fructose transporter GLUT5, which compensates for glucose deficiency. Notably, AML patients with upregulated transcription of the GLUT5-encoding gene SLC2A5 or increased fructose utilization have poor outcomes. Pharmacological blockage of fructose uptake ameliorates leukemic phenotypes and potentiates the cytotoxicity of the antileukemic agent, Ara-C...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27725288/a-23-years-follow-up-study-identifies-glut1-deficiency-syndrome-initially-diagnosed-as-complicated-hereditary-spastic-paraplegia
#10
Marina Diomedi, Ziv Gan-Or, Fabio Placidi, Patrick A Dion, Anna Szuto, Mario Bengala, Guy A Rouleau, Gian Luigi Gigli
Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) was initially described in the early 90s as a sporadic clinical condition, characterized by seizures, motor and intellectual impairment with variable clinical presentation, and without a known genetic cause. Although causative mutations in SLC2A1 were later identified and much more is known about the disease, it still remains largely underdiagnosed. In the current study, a previously described Italian family was re-analyzed using whole exome sequencing and clinically re-evaluated...
October 7, 2016: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/27703010/hepatic-zip14-mediated-zinc-transport-contributes-to-endosomal-insulin-receptor-trafficking-and-glucose-metabolism
#11
Tolunay Beker Aydemir, Catalina Troche, Min-Hyun Kim, Robert J Cousins
Zinc influences signaling pathways through controlled targeted zinc transport. Zinc transporter Zip14 KO mice display a phenotype that includes impaired intestinal barrier function with low grade chronic inflammation, hyperinsulinemia, and increased body fat, which are signatures of diet-induced diabetes (type 2 diabetes) and obesity in humans. Hyperglycemia in type 2 diabetes and obesity is caused by insulin resistance. Insulin resistance results in inhibition of glucose uptake by liver and other peripheral tissues, principally adipose and muscle and with concurrently higher hepatic glucose production...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27663513/phosphate-uptake-kinetics-and-tissue-specific-transporter-expression-profiles-in-poplar-populus%C3%A2-%C3%A3-%C3%A2-canescens-at-different-phosphorus-availabilities
#12
Mareike Kavka, Andrea Polle
BACKGROUND: Phosphorus (P) is a major plant nutrient. It is transported into and allocated inside plants by four families of phosphate transporters (PHT1 to PHT4) with high or low affinity to phosphate. Here, we studied whole-plant P uptake kinetics and expression profiles of members of the PHT families under high, intermediate and low P availability in the woody crop poplar (Populus × canescens) in relation to plant performance. RESULTS: Poplars exhibited strong growth reduction and increased P use efficiency in response to lower P availabilities...
2016: BMC Plant Biology
https://www.readbyqxmd.com/read/27642981/os-15-09-does-ace2-angiotensin-1-7-axis-protect-from-aging-associated-loss-of-skeletal-muscle-function
#13
Hikari Takeshita, Masao Takeda, Koichi Yamamoto, Hiromi Rakugi
OBJECTIVE: Angiotensin converting enzyme2 (ACE2), an enzyme that produces the Angiotensin 1-7(A1-7) from Angiotensin II, is considered to suppress organ damage by inhibition of the activation of renin-angiotensin system. We recently found that ACE2 deficiency in mice ameliorated insulin sensitivity of skeletal muscle with reduced expression of glucose transporter 4 and myocyte enhancer factor 2, an important transcription factor to maintain homeostasis of skeletal muscle. In this study, we investigated whether ACE2-A1-7 axis plays a protective role in aging-associated loss of skeletal muscle function in mice...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27637146/mtorc1-and-mtorc2-kinase-signaling-and-glucose-metabolism-drive-follicular-helper-t-cell-differentiation
#14
Hu Zeng, Sivan Cohen, Cliff Guy, Sharad Shrestha, Geoffrey Neale, Scott A Brown, Caryn Cloer, Rigel J Kishton, Xia Gao, Ben Youngblood, Mytrang Do, Ming O Li, Jason W Locasale, Jeffrey C Rathmell, Hongbo Chi
Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses...
September 20, 2016: Immunity
https://www.readbyqxmd.com/read/27577855/benzimidazole-derivative-small-molecule-991-enhances-ampk-activity-and-glucose-uptake-induced-by-aicar-or-contraction-in-skeletal-muscle
#15
Laurent Bultot, Thomas E Jensen, Yu-Chiang Lai, Agnete L B Madsen, Caterina Collodet, Samanta Kviklyte, Maria Deak, Arash Yavari, Marc Foretz, Sahar Ghaffari, Mohamed Bellahcene, Houman Ashrafian, Mark H Rider, Erik A Richter, Kei Sakamoto
AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β2)- and γ (γ1, γ2, γ3)-subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27568561/disruption-of-the-phosphate-transporter-pit1-in-hepatocytes-improves-glucose-metabolism-and-insulin-signaling-by-modulating-the-usp7-irs1-interaction
#16
Anne Forand, Eugénie Koumakis, Alice Rousseau, Yohann Sassier, Clément Journe, Jean-François Merlin, Christine Leroy, Valérie Boitez, Patrice Codogno, Gérard Friedlander, Isabelle Cohen
The liver plays a central role in whole-body lipid and glucose homeostasis. Increasing dietary fat intake results in increased hepatic fat deposition, which is associated with a risk for development of insulin resistance and type 2 diabetes. In this study, we demonstrate a role for the phosphate inorganic transporter 1 (PiT1/SLC20A1) in regulating metabolism. Specific knockout of Pit1 in hepatocytes significantly improved glucose tolerance and insulin sensitivity, enhanced insulin signaling, and decreased hepatic lipogenesis...
September 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27559173/%C3%AE-catenin-is-required-for-endothelial-cyp1b1-regulation-influencing-metabolic-barrier-function
#17
Nicole Ziegler, Khader Awwad, Beate Fisslthaler, Marco Reis, Kavi Devraj, Monica Corada, Simone Paolo Minardi, Elisabetta Dejana, Karl H Plate, Ingrid Fleming, Stefan Liebner
UNLABELLED: The canonical Wnt/β-catenin signaling pathway is crucial for blood-brain barrier (BBB) formation in brain endothelial cells. Although glucose transporter 1, claudin-3, and plasmalemma vesicular-associated protein have been identified as Wnt/β-catenin targets in brain endothelial cells, further downstream targets relevant to BBB formation and function are incompletely explored. By Affymetrix expression analysis, we show that the cytochrome P450 enzyme Cyp1b1 was significantly decreased in β-catenin-deficient mouse endothelial cells, whereas its close homolog Cyp1a1 was upregulated in an aryl hydrocarbon receptor-dependent manner, hence indicating that β-catenin is indispensable for Cyp1b1 but not for Cyp1a1 expression...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27554475/the-inactivation-of-rabgap-function-of-as160-promotes-lysosomal-degradation-of-glut4-and-causes-postprandial-hyperglycemia-and-hyperinsulinemia
#18
Bingxian Xie, Qiaoli Chen, Liang Chen, Yang Sheng, Hong Yu Wang, Shuai Chen
The AS160 is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers glucose transporter-4 (GLUT4) protein levels and causes severe insulin resistance. How its deficiency causes diminished GLUT4 proteins remains unknown. We found that deletion of AS160 decreased GLUT4 levels in a cell/tissue autonomous manner. Consequently, skeletal muscle-specific deletion of AS160 caused postprandial hyperglycemia and hyperinsulinemia. The pathogenic effects of AS160 deletion are mainly, if not exclusively, due to the loss of its RabGAP function since the RabGAP inactive AS160(R917K) mutant mice phenocopied the AS160 knockout mice...
August 23, 2016: Diabetes
https://www.readbyqxmd.com/read/27547921/fluorogenic-probes-reveal-a-role-of-glut4-n-glycosylation-in-intracellular-trafficking
#19
Shinya Hirayama, Yuichiro Hori, Zsolt Benedek, Tadashi Suzuki, Kazuya Kikuchi
Glucose transporter 4 (GLUT4) is an N-glycosylated protein that maintains glucose homeostasis by regulating the protein translocation. To date, it has been unclear whether the N-glycan of GLUT4 contributes to its intracellular trafficking. Here, to clarify the role of the N-glycan, we developed fluorogenic probes that label cytoplasmic and plasma-membrane proteins for multicolor imaging of GLUT4 translocation. One of the probes, which is cell impermeant, selectively detected exocytosed GLUT4. Using this probe, we verified the 'log' of the trafficking, in which N-glycan-deficient GLUT4 was transiently translocated to the cell membrane upon insulin stimulation and was rapidly internalized without retention on the cell membrane...
October 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27508154/glut2-proteins-and-ppar%C3%AE-transcripts-levels-are-increased-in-liver-of-ovariectomized-rats-reversal-effects-of-resistance-training
#20
Luciane M Tomaz, Marina R Barbosa, Zahra Farahnak, Cristiani G Lagoeiro, Natalia S S Magosso, Jean-Marc Lavoie, Sérgio E A Perez
PURPOSE: This study investigated the effects of ovariectomy (Ovx) and 12 weeks of resistance training (RT) on gene expression of GLUT2, the main glucose transporter in the liver, and on PPARγ, a transcription factor known to target GLUT2 expression. METHODS: Forty Holtzman rats were divided into 5 groups: Sham-sedentary (Sed), Sham- RT, Ovx-Sed, Ovx-RT, and Ovx-Sed with hormone replacement (E2). The RT protocol consisted of sessions held every 72 h for 12 weeks, during which the animals performed 4 to 9 vertical climbs (1...
June 2016: Journal of Exercise Nutrition & Biochemistry
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