Project description:Illuminating the mechanisms controlling glucose homeostasis may deepen our understanding of the pathogenesis of T2DM and provide new therapeutic strategies for T2DM in future. As reported, Dyrk1b is a pleiotropic protein and its genetic mutations associate with blood glucose levels. Yet, its role in glucose metabolism remains to be established. Herein, we invetigate the role of Dyrk1b in glucose metabolism and the underlying mechanisms. We find that hepatic Dyrk1b overexpression in mice impairs the glucose tolerance and insulin resistance, whereas global Dyrk1b deficiency improves glucose metabolism of mcie. Dyrk1b overexpression in vitro blunts insulin signalling and glucose uptake. Quantitative proteomic analyses further reveal that Wbp2 is a putative target of Dyrk1b. Importantly, hepatic Wbp2 restoration rescues the glucose homeostasis in Dyrk1b overexpression mice. Additionally, ATAC-seq analyses indicate Dyrk1b’s role in remodelling hepatic chromatin landscape. Collectively, our study uncovers a novel link between hepatic Dyrk1b and whole body glucose homeostasis via modulation of hepatic Wbp2 expression.
2025-05-29 | GSE234275 | GEO
Project description:RNA sequencing data of glucose treated microglia
Project description:The present study reports the gene expression data of Mycobacterium tuberculosis H37Rv and H37RvΔdosSΔdosT (DKO) grown on 0.2 % acetate/glucose under aerobic/hypoxic conditions. Acetate was reported to be present in granulomas of Mycobacterium tuberculosis infected guinea pigs which are also hypoxic. By exposing Mycobacterium tuberculosis H37Rv and H37RvΔdosSΔdosT to different combinations of granulomatous stresses (acetate/glucose and aerobic/hypoxic conditions) alongwith other experimental data, we were able to delineate a new signaling pathway that activates DevR (DosR) regulon through Acetyl phosphate. The presence of two pathways highlights the importance of targeting DevR and not DevS/DosT for intercepting DevRST signalling cascade.
Project description:Abstract: Glucose serves as a universal energy currency in living organisms, however, its potential non-energetic biomolecular functions are less well defined. Glucose was among the most increased analytes among >14,000 assessed across epidermal differentiation, an elevation verified in tissue engineered with fluorescent glucose sensors and also observed in differentiating cells from other tissues. Free glucose accumulation, but not its increased metabolism, was essential for epidermal differentiation and required GLUT1, GLUT3, and SLC5A1 transporters. Glucose affinity chromatography and azido-glucose click chemistry revealed direct glucose binding to a variety of regulatory proteins, including the IRF6 transcription factor (TF), whose epidermal knockout confirmed its requirement in glucose-dependent differentiation. Glucose binding mediated IRF6 dimerization, DNA affinity, and genomic targeting. The IRF6R84C mutant found in poorly differentiated cancers was unable to bind glucose. These data demonstrate a non-energetic role for glucose in modulating protein multimerization to control genome dynamics. Purpose: To determine the impact of glucose modulation on IRF6 genomic localization during keratinocyte differentiation
Project description:Abstract: Glucose serves as a universal energy currency in living organisms, however, its potential non-energetic biomolecular functions are less well defined. Glucose was among the most increased analytes among >14,000 assessed across epidermal differentiation, an elevation verified in tissue engineered with fluorescent glucose sensors and also observed in differentiating cells from other tissues. Free glucose accumulation, but not its increased metabolism, was essential for epidermal differentiation and required GLUT1, GLUT3, and SLC5A1 transporters. Glucose affinity chromatography and azido-glucose click chemistry revealed direct glucose binding to a variety of regulatory proteins, including the IRF6 transcription factor (TF), whose epidermal knockout confirmed its requirement in glucose-dependent differentiation. Glucose binding mediated IRF6 dimerization, DNA affinity, and genomic targeting. The IRF6R84C mutant found in poorly differentiated cancers was unable to bind glucose. These data demonstrate a non-energetic role for glucose in modulating protein multimerization to control genome dynamics. Purpose: To determine the impact of glucose modulation on chromatin accessibility during keratinocyte differentiation and the impact of IRF6 loss on chromatin accessibilty in differentiated keratincoytes
Project description:Illuminating the mechanisms controlling glucose homeostasis may deepen our understanding of the pathogenesis of T2DM and provide new therapeutic strategies for T2DM in future. As reported, Dyrk1b is a pleiotropic protein and its genetic mutations associate with blood glucose levels. Yet, the role of Dyrk1b in glucose metabolism is not well understood. Herein, we find that hepatic Dyrk1b overexpression in mice impairs the glucose tolerance and insulin resistance, whereas global Dyrk1b deficiency improves glucose metabolism of mcie. Dyrk1b overexpression in vitro blunts insulin signalling and glucose uptake. Collectively, our study uncovers a novel link between hepatic Dyrk1b and whole body glucose homeostasis.
Project description:Elucidation of the mechanisms controlling glucose homeostasis may deepen our understanding of the pathogenesis of T2DM and provide new therapeutic strategies for T2DM in the future. As reported, Dyrk1b is a pleiotropic protein and its genetic mutations are associated with blood glucose levels. However, the role of Dyrk1b in glucose metabolism is not well understood. Herein, we find that hepatic Dyrk1b overexpression in mice impairs the glucose tolerance and insulin resistance, whereas global Dyrk1b deficiency improves glucose metabolism of mcie. Dyrk1b overexpression in vitro blunts insulin signalling and glucose uptake. Collectively, our study uncovers a novel link between hepatic Dyrk1b and whole body glucose homeostasis.
Project description:Improving the early diagnosis and treatment of type 2 diabetes (T2D) can effectively control blood glucose. To investigate new long non-coding RNAs (lncRNAs) as molecular markers we used microarrays to identify differentially expressed lncRNAs and mRNAs in peripheral blood mononuclear cells from T2D patients and controls.