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glucose transporter 1 deficiency

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https://read.qxmd.com/read/30768374/aquaporin-3-deficiency-slows-cyst-enlargement-in-experimental-mouse-models-of-autosomal-dominant-polycystic-kidney-disease
#1
Weiling Wang, Xiaoqiang Geng, Lei Lei, Yingli Jia, Yingjie Li, Hong Zhou, Alan S Verkman, Baoxue Yang
Human autosomal dominant polycystic kidney disease (ADPKD) is characterized by bilateral renal cysts that lead to a decline in kidney function. Previous studies reported aquaporin (AQP)-3 expression in cysts derived from collecting ducts in ADPKD. To study the role of AQP3 in cyst development, we generated 2 polycystic kidney disease (PKD) mouse models: kidney-specific Pkd1 knockout mice and inducible Pkd1 knockout mice, each without and with AQP3 deletion. In both models, kidney sizes and cyst indexes were significantly reduced in AQP3-null PKD mice compared with AQP3-expressing PKD mice, with the difference seen mainly in collecting duct cysts...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30710049/mek2-negatively-regulates-lipopolysaccharide-mediated-il-1%C3%AE-production-through-hif-1%C3%AE-expression
#2
Harvinder Talwar, Mohamad Bouhamdan, Christian Bauerfeld, Jaya Talreja, Rifdat Aoidi, Nicolas Houde, Jean Charron, Lobelia Samavati
LPS-activated macrophages require metabolic reprogramming and glucose uptake mediated by hypoxia-inducible factor (HIF)-1 α and glucose transporter 1 (Glut1) expression for proinflammatory cytokine production, especially IL-1β. This process is tightly regulated through activation of MAPK kinases, including the MEK/ERK pathway as well as several transcription factors including HIF-1α. Although MAPK kinase (MEK) 2 deficiency had no significant effect on NO, TNF-α, or IL-12 production in response to LPS challenge, MEK2-deficient murine bone marrow-derived macrophages (BMDMs) exhibited lower IL-10 production...
February 1, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30700737/new-insights-into-glut1-mechanics-during-glucose-transfer
#3
Tatiana Galochkina, Matthieu Ng Fuk Chong, Lylia Challali, Sonia Abbar, Catherine Etchebest
Glucose plays a crucial role in the mammalian cell metabolism. In the erythrocytes and endothelial cells of the blood-brain barrier, glucose uptake is mediated by the glucose transporter type 1 (GluT1). GluT1 deficiency or mutations cause severe physiological disorders. GluT1 is also an important target in cancer therapy as it is overexpressed in tumor cells. Previous studies have suggested that GluT1 mediates solute transfer through a cycle of conformational changes. However, the corresponding 3D structures adopted by the transporter during the transfer process remain elusive...
January 30, 2019: Scientific Reports
https://read.qxmd.com/read/30660802/suppression-of-fatty-acid-%C3%AE-oxidation-and-energy-deficiency-as-a-cause-of-inhibitory-effect-of-e-coli-lipopolysaccharide-on-osmotic-water-transport-in-the-frog-urinary-bladder
#4
Ekaterina Fock, Elena Lavrova, Vera Bachteeva, Svetlana Nikolaeva, Rimma Parnova
Previously we showed that arginine-vasotocin (AVT)-stimulated osmotic water permeability (OWP) of the frog urinary bladder was decreased if the mucosal side of the bladder has been naturally colonized by Gram-negative bacteria, or if bacterial lipopolysaccharide (LPS) was introduced into the lumen of the isolated bladder (J. Exp. Zool., 2013, 319, 487-494). Taking into account that in different tissues and cell types, challenge with LPS causes significant metabolic shift and energy deficiency, we hypothesized that an LPS-induced decrease of AVT-stimulated OWP could depend on the reduction of fatty acid oxidation (FAO), which is important for generation of ATP in epithelia...
January 17, 2019: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://read.qxmd.com/read/30626647/failure-to-eliminate-a-phosphorylated-glucose-analog-leads-to-neutropenia-in-patients-with-g6pt-and-g6pc3-deficiency
#5
Maria Veiga-da-Cunha, Nathalie Chevalier, Xavier Stephenne, Jean-Philippe Defour, Nicole Paczia, Alina Ferster, Younes Achouri, Joseph P Dewulf, Carole L Linster, Guido T Bommer, Emile Van Schaftingen
Neutropenia represents an important problem in patients with genetic deficiency in either the glucose-6-phosphate transporter of the endoplasmic reticulum (G6PT/SLC37A4) or G6PC3, an endoplasmic reticulum phosphatase homologous to glucose-6-phosphatase. While affected granulocytes show reduced glucose utilization, the underlying mechanism is unknown and causal therapies are lacking. Using a combination of enzymological, cell-culture, and in vivo approaches, we demonstrate that G6PT and G6PC3 collaborate to destroy 1,5-anhydroglucitol-6-phosphate (1,5AG6P), a close structural analog of glucose-6-phosphate and an inhibitor of low- K M hexokinases, which catalyze the first step in glycolysis in most tissues...
January 22, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30623452/adipocyte-expression-of-glucose-transporter-1-and-4-in-pcos-relationship-to-insulin-mediated-and-noninsulin-mediated-whole-body-glucose-uptake
#6
Uche Ezeh, Ida Y-D Chen, Yen-Hao Chen, Ricardo Azziz
BACKGROUND: PCOS is a highly prevalent endocrine-metabolic disorder associated with insulin resistance (IR). In IR states noninsulin-mediated glucose uptake (NIMGU) may increase to compensate for declining insulin-mediated glucose uptake (IMGU), although this does not appear to be the case in PCOS. The underlying molecular mechanisms for this deficiency remains unclear. OBJECTIVES: To compare adipocyte glucose transporter 1 and 4 (GLUT-1 and GLUT-4) gene expression in PCOS women and matched controls, and to determine whether changes in GLUT-1 and GLUT-4 are associated with concomitant alterations in whole-body glucose uptake...
January 8, 2019: Clinical Endocrinology
https://read.qxmd.com/read/30616884/slc2a1-mutations-are-a-rare-cause-of-pediatric-onset-hereditary-spastic-paraplegia
#7
Francesco Nicita, Tommaso Schirinzi, Fabrizia Stregapede, Gessica Vasco, Enrico Bertini, Lorena Travaglini
SLC2A1 mutations cause glucose transporter type 1 deficiency syndrome, whose phenotypic spectrum is a continuum, ranging from classic to variant phenotypes, the latter accounting for about 10% of cases. Very few SLC2A1-mutated patients with a spastic paraplegia phenotype have been reported so far, and they are associated with paroxysmal choreo-athetosis (i.e., DYT9). The authors describe two sporadic children with pure and complex hereditary spastic paraplegia (HSP) without paroxysmal non-epileptic movement disorders harboring heterozygous de novo SLC2A1 pathogenic variants...
December 18, 2018: European Journal of Paediatric Neurology: EJPN
https://read.qxmd.com/read/30588498/development-of-a-rapid-functional-assay-that-predicts-glut1-disease-severity
#8
Sasha M Zaman, Saul A Mullen, Slavé Petrovski, Snezana Maljevic, Elena V Gazina, A Marie Phillips, Gabriel Davis Jones, Michael S Hildebrand, John Damiano, Stéphane Auvin, Holger Lerche, Yvonne G Weber, Samuel F Berkovic, Ingrid E Scheffer, Christopher A Reid, Steven Petrou
Objective: To examine the genotype to phenotype connection in glucose transporter type 1 (GLUT1) deficiency and whether a simple functional assay can predict disease outcome from genetic sequence alone. Methods: GLUT1 deficiency, due to mutations in SLC2A1 , causes a wide range of epilepsies. One possible mechanism for this is variable impact of mutations on GLUT1 function. To test this, we measured glucose transport by GLUT1 variants identified in population controls and patients with mild to severe epilepsies...
December 2018: Neurology. Genetics
https://read.qxmd.com/read/30575437/novel-role-of-the-er-sr-ca-2-sensor-stim1-in-regulation-of-cardiac-metabolism
#9
Helen E Collins, Betty M Pat, Luyun Zou, Silvio H Litovsky, Adam Raymond Wende, Martin E Young, John C Chatham
The ER/SR Ca2+ sensor, stromal interaction molecule 1 (STIM1), a key mediator of store-operated calcium entry, is expressed in cardiomyocytes and has been implicated in regulating multiple cardiac processes, including hypertrophic signaling. Interestingly, cardiomyocyte-restricted deletion of STIM1 (cr STIM1-KO) results in age-dependent ER stress, altered mitochondrial morphology, and dilated cardiomyopathy in mice. Here, we tested the hypothesis that STIM1 deficiency may also impact cardiac metabolism. Hearts isolated from 20-week old cr STIM1-KO mice exhibited a significant reduction in both oxidative and non-oxidative glucose utilization...
December 21, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://read.qxmd.com/read/30552304/interleukin-6-deficiency-modifies-the-effect-of-high-fat-diet-on-myocardial-expression-of-fatty-acid-transporters-and-myocardial-lipids
#10
P Mysliwiec, B Choromanska, M M Winnicka, K Kaminski, H Mysliwiec, J Dadan, E Supruniuk, A Chabowski
Chronic inflammation is a critical feature of obesity in the development of myocardial dysfunction. The observations that interleukin-6 (IL-6) is implicated in lipid and glucose homeostasis as well as its connection with the pathogenesis of insulin resistance might suggest the involvement of this cytokine in metabolic disorders of the failing heart. In the present study we aimed to assess the effects of IL-6 ablation in mice fed with normal and high fat diet on the myocardial expression of glucose and fatty acid transporting proteins, and to evaluate the paralleled alterations in lipid content...
August 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://read.qxmd.com/read/30502340/vitamin-d-deficiency-increases-blood-brain-barrier-dysfunction-after-ischemic-stroke-in-male-rats
#11
Iqbal Sayeed, Nefize Turan, Donald G Stein, Bushra Wali
Because vitamin D hormone deficiency (VDHdef ) can worsen severity and outcome for ischemic stroke, we examined the role of VDH in maintaining blood-brain-barrier (BBB integrity) in a rat model of stroke. In most types of stroke, the BBB is markedly compromised, potentially leading to a cascade of injury processes and functional deficits, so we examined a number of biomarkers associated with BBB disruption to determine whether VDH deficiency would further compromise the BBB following a stroke. Male Wistar rats were randomly assigned to one of two diet cohorts, VDH-sufficient (VDHsuf ) and VDHdef ...
February 2019: Experimental Neurology
https://read.qxmd.com/read/30446350/next-generation-sequencing-of-rna-reveals-novel-targets-of-resveratrol-with-possible-implications-for-canavan-disease
#12
Maja Dembic, Henriette S Andersen, Jean Bastin, Thomas K Doktor, Thomas J Corydon, Jörn Oliver Sass, Alexandra Lopes Costa, Fatima Djouadi, Brage S Andresen
Resveratrol (RSV) is a small compound first identified as an activator of sirtuin 1 (SIRT1), a key factor in mediating the effects of caloric restriction. Since then, RSV received great attention for its widespread beneficial effects on health and in connection to many diseases. RSV improves the metabolism and the mitochondrial function, and more recently it was shown to restore fatty acid β-oxidation (FAO) capacities in patient fibroblasts harboring mutations with residual enzyme activity. Many of RSV's beneficial effects are mediated by the transcriptional coactivator PGC-1α, a direct target of SIRT1 and a master regulator of the mitochondrial fatty acid oxidation...
October 22, 2018: Molecular Genetics and Metabolism
https://read.qxmd.com/read/30423260/hyperglycemia-promotes-microvillus-membrane-expression-of-dmt1-in-intestinal-epithelial-cells-in-a-pkc%C3%AE-dependent-manner
#13
Luqing Zhao, Thomas Bartnikas, Xiangpeng Chu, Janet Klein, Chris Yun, Shanthi Srinivasan, Peijian He
Excessive iron increases the incidence of diabetes and worsens diabetic complications. Reciprocally, diabetes induces iron loading, partially attributable to elevated intestinal iron export according to a recent report. Herein, we show that iron uptake and the mRNA expression of iron importer divalent metal transporter 1 (DMT1) were significantly increased in the duodenum of streptozotocin-induced diabetic mice. Immunofluorescence staining of human intestinal biopsies revealed increased brush border membrane (BBM) and decreased cytoplasmic DMT1 expression in patients with diabetes, suggesting translocation of DMT1...
November 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30401690/inhibitory-effects-of-vasostatin-1-against-atherogenesis
#14
Yuki Sato, Rena Watanabe, Nozomi Uchiyama, Nana Ozawa, Yui Takahashi, Remina Shirai, Kengo Sato, Yusaku Mori, Taka-Aki Matsuyama, Hatsue Ishibashi-Ueda, Tsutomu Hirano, Takuya Watanabe
Vasostatin-1,a chromogranin A-derived peptide (76 amino acids),is known to suppress vasoconstriction and angiogenesis.A recent study has shown that vasostatin-1 suppresses the adhesion of human U937 monocytes to human endothelial cells (HECs) via adhesion molecule downregulation. The present study evaluated the expression of vasostatin-1 in human atherosclerotic lesionsand its effects on inflammatory responses in HECs and human THP-1 monocyte-derived macrophages,macrophagefoam cell formation, migration and proliferation of human aortic smooth muscle cells (HASMCs) and extracellular matrix production by HASMCs, and atherogenesisin apolipoprotein E-deficient (ApoE-/- ) mice...
November 6, 2018: Clinical Science (1979-)
https://read.qxmd.com/read/30400014/gut-carbohydrate-inhibits-gip-secretion-via-a-microbiota-scfa-ffar3-pathway
#15
Eun-Young Lee, Xilin Zhang, Junki Miyamoto, Ikuo Kimura, Tomoaki Taknaka, Kenichi Furusawa, Takahito Jomori, Kosuke Fujimoto, Satoshi Uematsu, Takashi Miki
Mechanisms of carbohydrate-induced secretion of the two incretins namely glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are considered to be mostly similar. However, we found that mice exhibit opposite secretory responses in response to co-administration of maltose plus an α-glucosidase inhibitor miglitol (maltose/miglitol), stimulatory for GLP-1, as reported previously, but inhibitory for GIP. Gut microbiota was shown to be involved in maltose/miglitol-induced GIP suppression, as the suppression was attenuated in antibiotics (Abs)-treated mice and abolished in germ-free mice...
December 1, 2018: Journal of Endocrinology
https://read.qxmd.com/read/30320424/characteristic-proton-magnetic-resonance-spectroscopy-in-glucose-transporter-type-1-deficiency-syndrome
#16
Manami Akasaka, Atsushi Kamei, Nami Araya, Kotaro Oyama, Makoto Sasaki
No abstract text is available yet for this article.
October 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
https://read.qxmd.com/read/30301464/profile-of-cardiac-lipid-metabolism-in-stz-induced-diabetic-mice
#17
Wenjie Li, Min Yao, Ruonan Wang, Yun Shi, Lianguo Hou, Ziyuan Hou, Kaoqi Lian, Nan Zhang, Yaqi Wang, Weiwei Li, Wei Wang, Lingling Jiang
BACKGROUND: Lipotoxicity contributes to diabetic myocardial disease. In this study, we investigated the lipid species contributing to lipotoxicity and the relationship with peroxisomal β-oxidation in the heart of diabetic mice. METHODS: Male C57BL/6 mice were randomly divided into a Diabetic group (intraperitoneal injection of STZ) and a Control group (saline). Cardiac function indexes [ejection fraction (EF%) and fractional shortening (FS%)] were evaluated by echocardiography...
October 9, 2018: Lipids in Health and Disease
https://read.qxmd.com/read/30290217/novel-abca1-peptide-agonists-with-antidiabetic-action
#18
Salman Azhar, Stefanie Bittner, Jie Hu, Wen-Jun Shen, Yuan Cortez, Xiao Hao, Han Lu, Jens O Lagerstedt, Fredric B Kraemer, Jan O Johansson
Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice...
October 2, 2018: Molecular and Cellular Endocrinology
https://read.qxmd.com/read/30271476/rare-and-treatable-cause-of-early-onset-refractory-absence-seizures
#19
Gajanan A Panandikar, Sangeeta H Ravat, Rahil R Ansari, Karan M Desai
Glut-1 transporter deficiency syndrome (GLUT1-DS) is a rare disorder caused by the mutation in SLC2A1 gene, which results in impaired glucose transport into the brain. It has a broad spectrum of phenotypic presentation ranging from cognitive decline, microcephaly, and refractory seizures to complex movement disorder. Recognition of this disorder is necessary as it is refractory to antiepileptic drugs (AEDs) and responds significantly to ketogenic diet. We report a case of 7-year-old girl who presented with paroxysmal eye movements in infancy with early-onset absence epilepsy (EOAE), which worsened in early morning and on fasting and was found to be refractory to four AEDs...
July 2018: Journal of Pediatric Neurosciences
https://read.qxmd.com/read/30226996/insulin-regulates-glut4-in-the-ventromedial-hypothalamus-to-restore-the-sympathoadrenal-response-to-hypoglycemia-in-diabetic-rats
#20
Rahul Agrawal, Adriana Vieira-de-Abreu, Griffin Durupt, Casey Taylor, Owen Chan, Simon J Fisher
It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-diabetic Sprague-Dawley rats were infused with either insulin (3mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 weeks and compared to nondiabetic rats. Rats underwent hyperinsulinemic (50 mU.kg-1 .min-1 ) hypoglycemic (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia noted by an high glucose infusion rate (GIR) and blunted epinephrine and glucagon responses...
September 18, 2018: American Journal of Physiology. Endocrinology and Metabolism
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