Effect of metformin in the mouse ileum gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE271623 | GEO | 2025/08/22
REPOSITORIES: GEO
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2016-07-15 | GSE80436 | GEO
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Project description:Variation in the Glucose Transporter gene SLC2A2 is associated with glycaemic response to metformin
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2020-06-16 | GSE138756 | GEO
Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.
2020-06-16 | GSE138754 | GEO
Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.
2020-06-16 | GSE138755 | GEO
Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.
2020-06-16 | GSE138753 | GEO
Project description:The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR mediated gene editing of immortalized erythroblasts and adult CD34 hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signaling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anemia in GLUT1 deficiency syndrome.
2024-02-29 | MSV000094204 | MassIVE
Project description:Glucose transporter 2 (GLUT2) is a key player in the regulation of glucose dynamics in organs central to metabolism, namely the liver, pancreas and intestine In humans, mutations of the GLUT2 gene (Fanconi-Bickel syndrome) cause important defects in glucose homeostasis. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, to date it is still unclear which role it plays in the brain. In this regard, in order to shed some light on the function of GLUT2 in the vertebrate brain, we have knocked down the functional ortholog of human GLUT2 in zebrafish. Our results show that abrogation of glut2 in vivo leads to defective brain organogenesis coinciding with reduced glucose uptake and increased programmed cell death in the brain region. Interestingly, coinciding with the observed localization of glut2 expression in the hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a that are the source of glutamatergic and GABAergic neurons, respectively. In addition, progenitor cells expressing neurod, a marker for immature and mature granule cells, were not affected by the lack of glut2. Furthermore, transcriptome analysis of glut2 knockdown embryos supports the notion that the lack of glut2 impacts brain development. Overall, the results of this study highlight the physiological relevance of glut2 in glucose uptake and availability during brain development, supporting the important role of glut2 in brain glucose sensing, and demonstrate the usefulness of a novel in vivo model of GLUT2 deficiency.
2014-12-23 | GSE57836 | GEO