Kinetic model incorporating glucose transport inhibition (vanniekerk1)
Ontology highlight
ABSTRACT:
SUBMITTER: Dawie van Niekerk
PROVIDER: 175 | FAIRDOMHub | 2015-11-23
REPOSITORIES: FAIRDOMHub
Similar Datasets
Project description:Glucose Transport Dependency Defines a Therapeutic Vulnerability in Myeloproliferative Neoplasms
| PRJNA1425924 | ENA
Project description:The glucose dual-affinity transport system (low- and high-affinity) is a conserved strategy exerted by microorganisms to cope with the naturally fluctuating availability of nutrients in the environment. The glucose sensing and uptaking process were believed to be tightly involved in cellulases expression regulation in cellulolytic fungi. However, both the identities and functions of the major molecular components of this evolutionarily conserved system in filamentous fungi remain elusive. Here, we conducted a systematic identification and characterization of the glucose dual-affinity transport system in the model fungus Neurospora crassa. Using RNA sequencing coupled with functional transport analyses, we were able to assign GLT-1 (Km = 18.42 ± 3.38 mM) and HGT-1/-2 (Km = 16.13 ± 0.95 µM and 98.97 ± 22.02 µM) to low- and high-affinity glucose transport systems, respectively. The high-affinity transporters hgt-1/-2 were able to complement a moderate growth defect under high glucose when glt-1 was deleted. Simultaneous deletion of hgt-1/-2 led to extensive derepression of genes for plant cell wall deconstruction on cellulose. This suppression by HGT-1/-2 was connected to both carbon catabolite repression (CCR) and the cyclic adenosine monophosphate-protein kinase A pathway. Alteration of a residue conserved across taxa for hexose-transporters was found to result in a loss of glucose-transporting function, whereas CCR signal transduction was retained, indicating a dual function for HGT-1/-2 as “transceptors”. In this study, GLT-1 and HGT-1/-2 are identified as the key components of the glucose dual-affinity transport system, which play diverse roles in glucose transport and carbon metabolism. Given their wide conservation across fungal species, the glucose dual-affinity transport components and their pleiotropic roles revealed in this study would shed extensive new light on the molecular basis of nutrient transport, signaling, and plant cell wall degradation in fungi.
2017-01-04 | GSE78952 | GEO
Project description:Analytical kinetic model of native tandem promoters in E. coli
| PRJNA759250 | ENA
Project description:Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an
integrative model
| 5b8 | Physiome Model Repository
Project description:Metformin is among the most prescribed anti-diabetic drugs, but the primary molecular mechanism by which metformin lowers blood glucose levels is unknown. Previous studies have proposed numerous mechanisms by which acute metformin lowers blood glucose, including the inhibition of mitochondrial complex I of the electron transport chain (ETC). Here, we used transgenic mice that globally express the Saccharomyces cerevisiae protein NDI1 to determine whether the glucose lowering effect of acute oral administration of metformin requires inhibition of mitochondrial complex I of the ETC in vivo. NDI1 is a yeast NADH dehydrogenase enzyme that complements the loss of mammalian mitochondrial complex I electron transport function and is insensitive to pharmacologic mitochondrial complex I inhibitors including metformin. We demonstrate that NDI1 expression attenuates metformin’s ability to lower blood glucose levels under standard chow and high-fat diet conditions. Our results indicate that acute oral administration of metformin targets mitochondrial complex I to lower blood glucose.
2024-10-12 | GSE278099 | GEO
Project description:Pharmacological inhibition of lipid import and transport proteins in ovarian cancer
| PRJNA876913 | ENA
Project description:Prolonged cultivation of Saccharomyces cerevisiae in aerobic, glucose-limited chemostat cultures (dilution rate, 0·10 hâ1) resulted in a progressive decrease of the residual glucose concentration (from 20 to 8 mg lâ1 after 200 generations). This increase in the affinity for glucose was accompanied by a fivefold decrease of fermentative capacity, and changes in cellular morphology. These phenotypic changes were retained when single-cell isolates from prolonged cultures were used to inoculate fresh chemostat cultures, indicating that genetic changes were involved. Kinetic analysis of glucose transport in an âevolvedâ strain revealed a decreased Km, while Vmax was slightly increased relative to the parental strain. Apparently, fermentative capacity in the evolved strain was not controlled by glucose uptake. Instead, enzyme assays in cell extracts of the evolved strain revealed strongly decreased capacities of enzymes in the lower part of glycolysis. This decrease was corroborated by genome-wide transcriptome analysis using DNA microarrays. In aerobic batch cultures on 20 g glucose lâ1, the specific growth rate of the evolved strain was lower than that of the parental strain (0·28 and 0·37 hâ1, respectively). Instead of the characteristic instantaneous production of ethanol that is observed when aerobic, glucose-limited cultures of wild-type S. cerevisiae are exposed to excess glucose, the evolved strain exhibited a delay of 90 min before aerobic ethanol formation set in. This study demonstrates that the effects of selection in glucose-limited chemostat cultures extend beyond glucose-transport kinetics. Although extensive physiological analysis offered insight into the underlying cellular processes, the evolutionary âdriving forceâ for several of the observed changes remains to be elucidated Experiment Overall Design: A crucial feature of bakers' yeast is its capacity to produce CO2, referred to as fermentative capacity (van Hoek et al., 1998). After prolonged glucose-limited cultivation of S. cerevisiae, in addition to an increased affinity for glucose, we observed a dramatic decrease in fermentative capacity. Consequently, the aim of the present study was to perform an integral analysis of the long-term adaptation of S. cerevisiae during prolonged glucose-limited, aerobic cultivation in chemostat cultures, with special emphasis on the regulation of glucose transport and glycolytic capacity. To this end, we applied an integrated approach that combined transcriptome analysis, measurement of fermentative capacity and activities of glucose transport and glycolytic enzymes, and characterization of cellular morphology.
2008-06-16 | E-GEOD-8898 | biostudies-arrayexpress
Project description:Prolonged cultivation of Saccharomyces cerevisiae in aerobic, glucose-limited chemostat cultures (dilution rate, 0·10 h–1) resulted in a progressive decrease of the residual glucose concentration (from 20 to 8 mg l–1 after 200 generations). This increase in the affinity for glucose was accompanied by a fivefold decrease of fermentative capacity, and changes in cellular morphology. These phenotypic changes were retained when single-cell isolates from prolonged cultures were used to inoculate fresh chemostat cultures, indicating that genetic changes were involved. Kinetic analysis of glucose transport in an ‘evolved’ strain revealed a decreased Km, while Vmax was slightly increased relative to the parental strain. Apparently, fermentative capacity in the evolved strain was not controlled by glucose uptake. Instead, enzyme assays in cell extracts of the evolved strain revealed strongly decreased capacities of enzymes in the lower part of glycolysis. This decrease was corroborated by genome-wide transcriptome analysis using DNA microarrays. In aerobic batch cultures on 20 g glucose l–1, the specific growth rate of the evolved strain was lower than that of the parental strain (0·28 and 0·37 h–1, respectively). Instead of the characteristic instantaneous production of ethanol that is observed when aerobic, glucose-limited cultures of wild-type S. cerevisiae are exposed to excess glucose, the evolved strain exhibited a delay of 90 min before aerobic ethanol formation set in. This study demonstrates that the effects of selection in glucose-limited chemostat cultures extend beyond glucose-transport kinetics. Although extensive physiological analysis offered insight into the underlying cellular processes, the evolutionary ‘driving force’ for several of the observed changes remains to be elucidated Keywords: evolution
2007-08-31 | GSE8898 | GEO
Project description:RNA-binding proteins play a key role in shaping gene expression profiles during stress, however, little is known about the dynamic nature of these interactions and how this influences the kinetics of gene expression. To address this, we developed kinetic χCRAC, a UV cross-linking method that enabled us to quantitatively measure the dynamics of protein-RNA interactions in vivo on a minute time-scale. Here, using kinetic χCRAC we measure the global RNA-binding dynamics of the yeast transcription termination factor Nab3 in response to glucose starvation. These measurement reveal rapid changes in protein-RNA interactions within one minute following stress imposition. Changes in Nab3 binding are largely independent of alterations in transcription rate during the early stages of stress response, indicating orthogonal transcriptional control mechanisms. We also uncover a function for Nab3 in dampening expression of stress-responsive genes. Kinetic χCRAC has the potential to greatly enhance our understanding of in vivo dynamics of protein-RNA interactions.
2017-04-11 | GSE85545 | GEO
Project description:Hyperglycemia-induced damage to bone formations and function has been recognized.However, as the largest connective tissue organ, whether bone and osteocytes in turn regulate blood sugar and insulin sensitivity has not been addressed. Here we identified a novel protein termed intraflagellar transport 140 with functional importance in regulating osteogenesis, which is also related to the osteoblastic insulin sensitivity. We established Ift140 osteoblastic conditional knockout mice model, and found that blood glucose metabolism could be regulated through osteoblastic IFT140 interacting with O-GlcNAc transferase to regulate insulin signaling. The discovery provides new insight for two-way regulation between bone and glucose metabolism, and also exploring potential new target for blood glucose interventions.
2021-06-24 | GSE178558 | GEO