Decreased GLUT2 expression and defective glucose uptake in MODY3 human iPSC-Derived beta cells
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PROVIDER: PRJNA587120 | ENA |
REPOSITORIES: ENA
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Project description:Decreased GLUT2 expression and defective glucose uptake in MODY3 human iPSC-derived beta cells
| PRJNA588792 | ENA
Project description:Transcriptomic analysis of E. coli strains with impaired glucose uptake capacity
| PRJEB32273 | ENA
Project description:To evaluate the impact of HNF1A+/H126D mutation on pancreatic beta cell biology, we performed RNA-Seq analyses on the day 20 endocrine progenitor cells which maximally expressed HNF1A. Principal component analysis (PCA) plot showed distinct clustering of WT cells separate from the mutant cells, indicating that the HNF1A+/H126D mutation has an impact on global transcript profiles in the cells. A volcano plot demonstrated that there were 1724 genes downregulated and only 583 genes upregulated in mutant cells as compared to WT cells. Gene ontology (GO) analysis revealed that the genes that were downregulated in mutant cells were largely involved in biological processes such as localization, transport and secretion and molecular functions such as protein binding and transporter activity.
2021-03-22 | GSE140208 | GEO
Project description:Purpose: To investigate the impact of HNF1A mutation on the development of pancreatic endocrine progenitors using differentiated control and MODY3-hiPSCs Methods: ChIP-Seq was performed on pancreatic endocrine progenitors obtained on day 20 of the directed differentiation of control hPSCs (1 clone from H9 and 3 clones from iAgB-hiPSC) and hiPSCs from MODY3 patients (3 clones from P2. Peak calling analyses were carried out. qRT-PCR validation was also performed using SYBR Green assays. Results: ChIP-Seq analysis revealed that numerous HNF1A target genes were downregulated in MODY3-hiPSC-derived pancreatic endocrine progenitors. Altered expression of a number of genes were further confirmed with qRT-PCR. Conclusions: The H126D mutation in HNF1A does not affect the expression levels of HNF1A. However, this mutation affects the DNA binding capability of the transcription factor, thereby resulting in deficiency in the gene expression of proteins that are essential to maintain normal human beta-cell function for insulin secretion.
2021-03-22 | GSE139832 | GEO
Project description:Rationale: Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate receptors ERα and ERβ. Since female sex hormones enhance global glucose utilization and because myocardial function and mass are tightly linked to cardiac glucose metabolism we tested the hypothesis that expression and activation of the estrogen receptor α (ERα) might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Methods and Results: Cardiac glucose uptake quantified in vivo by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was strongly impaired in ovarectomized compared to gonadal intact female C57BL/6JO mice. The selective ERα agonist 16α-LE2 and the non-selective ERα and ERβ agonist 17β-estradiol completely restored cardiac glucose uptake in ovarectomized mice. Cardiac FDG uptake was strongly decreased in female ERα knockout mice (ERKO) compared to wild type littermates. Biochemical assays, affymetrix cDNA array analysis, western blotting and immuno-staining of cardiac glucose transporters revealed a positive correlation of ERα dependent cardiac FDG uptake with preserved cardiac glucose transporter-1 expression and micro-vascular localization. Conclusions: Systemic activation of the ERα estrogen receptor is sufficient and its expression is required to maintain physiological glucose uptake in the murine heart, which is likely to contribute to known cardio-protective estrogen effects. total samples analysed are 20
2012-12-20 | E-GEOD-34807 | biostudies-arrayexpress
Project description:Insulin action in adipocytes affects whole-body insulin sensitivity. Studies of adipose-specific Glut4 knockout mice have established that adipose Glut4 contributes to the control of systemic glucose homeostasis. Presumably, this reflects a role for Glut4-mediated glucose transport in the regulation of secreted adipokines. In cultured 3T3-L1 adipocytes, Rab10 GTPase is required for insulin-stimulated translocation of Glut4 (Sano et al., 2007). The physiological importance of adipose Rab10 and the significance of its role in the control of Glut4 vesicle trafficking in vivo are unknown. Here we report that adipocytes from adipose-specific Rab10 knockout mice have a ~50% reduction in glucose uptake and Glut4 translocation to the cell surface in response to insulin, demonstrating a role for Rab10 in Glut4 trafficking. Moreover, hyperinsulinemic-euglycemic clamp shows decreased whole-body glucose uptake as well as impaired suppression of hepatic glucose production in adipose Rab10 knockout mice. Thus, fully functional Glut4 vesicle trafficking in adipocytes is critical for maintaining insulin sensitivity. Comparative transcriptome analysis of perigonadal adipose tissue demonstrates significant transcriptional similarities between adipose Rab10 knockout mice and adipose Glut4 knockout mice, consistent with the notion that the phenotypic similarities between the two models are mediated by reduced insulin-stimulated glucose transport into adipocytes. Transcriptome sequencing of perigonadal white adipose tissue
2016-06-30 | E-GEOD-70123 | biostudies-arrayexpress
Project description:Rationale: Estrogens attenuate cardiac hypertrophy and increase cardiac contractility via their cognate receptors ERα and ERβ. Since female sex hormones enhance global glucose utilization and because myocardial function and mass are tightly linked to cardiac glucose metabolism we tested the hypothesis that expression and activation of the estrogen receptor α (ERα) might be required and sufficient to maintain physiological cardiac glucose uptake in the murine heart. Methods and Results: Cardiac glucose uptake quantified in vivo by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was strongly impaired in ovarectomized compared to gonadal intact female C57BL/6JO mice. The selective ERα agonist 16α-LE2 and the non-selective ERα and ERβ agonist 17β-estradiol completely restored cardiac glucose uptake in ovarectomized mice. Cardiac FDG uptake was strongly decreased in female ERα knockout mice (ERKO) compared to wild type littermates. Biochemical assays, affymetrix cDNA array analysis, western blotting and immuno-staining of cardiac glucose transporters revealed a positive correlation of ERα dependent cardiac FDG uptake with preserved cardiac glucose transporter-1 expression and micro-vascular localization. Conclusions: Systemic activation of the ERα estrogen receptor is sufficient and its expression is required to maintain physiological glucose uptake in the murine heart, which is likely to contribute to known cardio-protective estrogen effects.
2012-12-20 | GSE34807 | GEO
Project description:Microglia is dynamically reprogrammed according to the progression of Alzheimer’s disease (AD). However, clinical translation into biomarker development for functional change in microglia has not been achieved. Here, we find the close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake, which can be noninvasively estimated by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). We found that increased FDG activity in the hippocampus of an AD mouse model depended on microglial uptake. Single-cell RNA-sequencing of the hippocampus showed the changes of glucose metabolism profiles including glucose transporters, glycolysis and oxidative phosphorylation mainly occurred in microglia. A subset of microglia with high glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. Furthermore, we also found a positive association between a soluble TREM2 of cerebrospinal fluid, a marker of microglial activation, and hippocampal FDG uptake as a human study. We identified a reconfiguration of microglial glucose metabolism in the hippocampus of AD and suggested a feasible imaging biomarker based on widely used FDG PET to reflect microglial metabolic profiles.
2021-09-08 | GSE150934 | GEO
Project description:Insulin action in adipocytes affects whole-body insulin sensitivity. Studies of adipose-specific Glut4 knockout mice have established that adipose Glut4 contributes to the control of systemic glucose homeostasis. Presumably, this reflects a role for Glut4-mediated glucose transport in the regulation of secreted adipokines. In cultured 3T3-L1 adipocytes, Rab10 GTPase is required for insulin-stimulated translocation of Glut4 (Sano et al., 2007). The physiological importance of adipose Rab10 and the significance of its role in the control of Glut4 vesicle trafficking in vivo are unknown. Here we report that adipocytes from adipose-specific Rab10 knockout mice have a ~50% reduction in glucose uptake and Glut4 translocation to the cell surface in response to insulin, demonstrating a role for Rab10 in Glut4 trafficking. Moreover, hyperinsulinemic-euglycemic clamp shows decreased whole-body glucose uptake as well as impaired suppression of hepatic glucose production in adipose Rab10 knockout mice. Thus, fully functional Glut4 vesicle trafficking in adipocytes is critical for maintaining insulin sensitivity. Comparative transcriptome analysis of perigonadal adipose tissue demonstrates significant transcriptional similarities between adipose Rab10 knockout mice and adipose Glut4 knockout mice, consistent with the notion that the phenotypic similarities between the two models are mediated by reduced insulin-stimulated glucose transport into adipocytes.
2016-06-30 | GSE70123 | GEO
Project description:Saccharomyces cerevisiae developed elegant mechanisms to monitor nutrient availability and trigger adaptative responses to nutrient deficiency. Nutrient sensing requires close coordination of cell surface sensors with intracellular mechanisms. This yeast senses the presence of glucose by two modified hexose transporters, Rgt2 and Snf3 (regulating expression of genes encoding hexose transporters) and the G-protein coupled receptor Gpr1 (modulating Protein Kinase A (PKA) activity).. It has been difficult to differentiate between cellular responses mediated by cell surface and intracellular sensors, respectively. Using a strain that is devoid of glucose uptake, we show that the mere presence of glucose does not elicit any glucose-dependent transcriptional responses. This indicates that signals generated by surface sensors are not sufficient to mediate glucose-dependent transcriptional responses. Instead, intracellular glucose or metabolites derived from it are required for transcriptional changes associated with glucose exposure. We used microarrays from biological triplicate samples to measure the global transcriptional response to sudden addition of glucose to yeast cells growing at steady state on ethanol. The experiment was conducted using a strain that is devoid of glucose uptake and compared with an isogenic strain.
2010-03-02 | GSE20566 | GEO