MicroRNA-21 Promotes Pancreatic β cell Function through Modulating Glucose Uptake
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ABSTRACT:
PROVIDER: PRJNA790098 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17267974.fastq.gz | Fastqsanger.gz | |||
| SRR17267975.fastq.gz | Fastqsanger.gz | |||
| SRR17267976.fastq.gz | Fastqsanger.gz | |||
| SRR17267977.fastq.gz | Fastqsanger.gz | |||
| SRR17267978.fastq.gz | Fastqsanger.gz |
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Project description:Pancreatic β cell dysfunction greatly contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we studied the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their β cells (miR-21βKO). We found that miR-21βKO mice developed glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies revealed that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets resulted in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrated that delivery of miR-21 into the pancreas of type 2 diabetic db/db mice is able to promote Glut2 expression and significantly reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes insulin secretion and support a role for miR-21 in the adaptation of pancreatic β cell function in type 2 diabetes.
2022-05-16 | GSE191194 | GEO
Project description:Pancreatic β cell dysfunction contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their β cells (miR-21βKO). We find that miR-21βKO mice develop glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies reveal that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets results in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic db/db male mice is able to promote Glut2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes.
| S-EPMC9213410 | biostudies-literature
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
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. The CEN.PK strain was used in this research. A strain with all known hexose transporters deleted (Null strain) was compared with an isogenic reference. The two strains were grown in a chemostat (D = 0.1 h-1) using ethanol as the carbon source. Transcriptional responses between the strains were measured in biological triplicates at steady state and then pulsed with glucose at time t = 0. Transcriptional response was measured again after t = 20 min to determine changes in gene expression changes only in response to the presence of glucose.
2010-03-06 | E-GEOD-20566 | biostudies-arrayexpress
Project description:Adjudin improves beta cell maturation, hepatic glucose uptake and glucose homeostasis
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Project description:Listeria monocytogenes (Lm) strains expressing high levels of the virulence regulator PrfA (mutant PrfA* or wild-type PrfA) show strong growth inhibition in minimal media when supplemented with glucose but not when supplemented with glucose-6-phosphate compared to the isogenic strains expressing low levels of PrfA. A significantly reduced rate of glucose uptake is observed in the PrfA* over-expressing strain growing in LB supplemented with glucose. Comparative transcriptome analyses were performed with RNA isolated from a prfA mutant and the isogenic strain carrying multiple prfA or prfA* copies on a plasmid. The analysis reveals in addition to high transcriptional up-regulation of the known PrfA-regulated virulence genes (group I), less pronounced up-regulation in the expression of several phage- and metabolic genes (group II) and strong down-regulation of several genes involved mainly in carbon- and nitrogen- metabolism in the PrfA* over-expressing strain (group III). Among the latter genes are in particular the nrgAB-, gltAB-, glnRA- (involved in nitrogen metabolism), ilvB- operons (involved in biosynthesis of the branched chain amino acids) and genes for some ABC transporters. Most of the down-regulated genes have been shown previously in Bacillus subtilis to belong to a class of genes whose expression is negatively affected by impaired glucose uptake. The results lead to the conclusion that excess PrfA(*) interferes with component(s) essential for PTS-mediated glucose transport. Keywords: Metabolism and Virulence gene expression
2006-05-01 | GSE4414 | GEO
Project description:Transcriptomic analysis of E. coli strains with impaired glucose uptake capacity
| PRJEB32273 | ENA
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