Mus sp.
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ABSTRACT:
PROVIDER: PRJNA384348 | ENA |
REPOSITORIES: ENA
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Project description:Dipeptidyl peptidase-4 (Dpp4) inhibitors are used worldwide to combat diabetes, however, their roles in cardiovascular disorders are yet to be defined. Here we show that a DPP4 inhibitor, linagliptin, contributes for the suppression of capillary rarefaction in cardiac tissues of dietary obese mice model. Imposing a high fat diet into mice induced capillary rarefaction and cardiac dysfunction. These pathologies associated with high DPP4 level in circulation, and the administration of linagliptin into dietary obese mice suppressed the development of capillary rarefaction and ameliorated cardiac dysfunction. Early growth response protein 1 (EGR1), known as an angiogenic transcription factor, is significantly reduced in the cardiac tissue upon metabolic stress, and this suppression was inhibited by the administration of linagliptin.
2017-04-27 | GSE98226 | GEO
Project description:Effect of expression of dipeptidyl peptidase-IV (DPP-IV) in U373 cell line on uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix.
2011-12-31 | E-MTAB-583 | biostudies-arrayexpress
Project description:The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Background: Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for a proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the en-zyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Methods: Transcriptome analysis was performed comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily, and the reti-nas of 10 additional db/db mice that received vehicle eye drops. 10 non diabetic mice (db/+) were used as control group. Gene Ontology (GO) and Reactome databases were used to assess the Gene Set Enrichment Analysis (GSEA) in order to explore the most enriched biological pathways among groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Results: Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission was the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesi-cle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of macromolecule biosynthetic process with positive regulation of cell communication which provides beneficial effects for neuronal metabolism. Conclu-sions: This study suggests that topical administration of sitagliptin ameliorates the abnormali-ties on presynaptic and postsynaptic signal transmission during experimental DR, and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.
2023-01-11 | GSE219084 | GEO
Project description:Dipeptidyl peptidase 4 inhibitoralogliptinimproves health and survivalof mice on a high-fat diet
| PRJNA427240 | ENA
Project description:Covalent chemical probes and drugs combine unique pharmacologic properties with the availability of straightforward compound profiling technologies via chemoproteomic platforms. These advantages have fostered the development of suitable electrophilic ‘warheads’ for systematic covalent chemical probe discovery. Despite undisputable advances in the last years, the targeted development of proteome-wide selective covalent probes such as for dipeptidyl peptidase (DPP) 8 and 9 (DPP8/9), intracellular serine hydrolases of the pharmacologically relevant dipeptidyl peptidase 4 activity/structure homologues (DASH) family, however, remains a challenge. Here, we show the exploration of the natural product Sulphostin, a DPP4 inhibitor, as a starting point for DPP8/9 inhibitor development. The generation of Sulphostin-inspired N-phosphonopiperidones leads to derivatives with improved DPP8/9 inhibitory potency, an enhanced proteome-wide selectivity and confirmed DPP8/9 engagement in cells, thereby representing that structural fine-tuning of the warhead’s leaving group may represent a straightforward strategy for achieving target selectivity in exoproteases such as DPPs.
2025-02-25 | PXD058896 | Pride
Project description:MicroRNAs (miRNAs) are essential regulators involved in multiple biological processes. To achieve their gene repression function, they are loaded in miRNA-specific Argonautes to form the miRNA-induced silencing complex (miRISC). Mammalians and C. elegans intriguingly possess more than one paralog of miRNA-specific Argonautes and the dynamic between them remains unclear. Here, using C. elegans as a model system, we report dipeptidyl peptidase DPF-3 as a new interactor of miRNA-specific Argonautes ALG-1 and ALG-2. Knockout of dpf-3 rescues miRNA-related defects observed in alg-1 null animals and allows ALG-2 to better compensate for the lack of its paralog through higher expression and activity. While DPF-3 can cleave a N-terminal dipeptide of ALG-2 in vitro, we show that it is likely not the molecular mechanism used by DPF-3 to regulate ALG-2. This study uncovers the importance of a dipeptidyl peptidase in the miRNA pathway and provide insights in miRNA-specific Argonautes regulation dynamics in animals.
2025-03-06 | GSE276186 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36716: Muscle Involvement in Preservation of Metabolic Flexibility by Treatment using n-3 PUFA or Rosiglitazone in Dietary-Obese Mice GSE36717: Muscle Involvement in Preservation of Metabolic Flexibility by a Combination Treatment using n-3 PUFA and Rosiglitazone in Dietary-Obese Mice Refer to individual Series
2012-09-07 | E-GEOD-36718 | biostudies-arrayexpress
Project description:PCN, a selective murine PXR agonist, was administered to obese mice with the goal to investigate what transcriptional changes PXR activation cause in the livers of obese mice.
2021-08-06 | GSE136667 | GEO
Project description:The study objective was to determine differentially expressed mRNA transcripts in cardiac tissues from E18.5 fetal mice e born to obese dams fed a high fat/high sugar diet and control dams fed normal diet.
2021-09-01 | GSE180763 | GEO
Project description:Elevated circulating dipeptidyl-peptidase 4 (DPP4) is a biomarker for liver disease, but its involvement in gluconeogenesis and metabolic associated fatty liver disease (MAFLD) progression remains unclear. Here we identified that DPP4 in hepatocytes but not Tie2+ endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 (Dpp4-/-) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of Dpp4-/- mice displayed enrichment for inflammasome, p53, and senescence programs compared to littermate controls. High-fat high-cholesterol (HFHC)-feeding decreased Dpp4 expression in F4/80+ cells, with only minor changes in immune signaling.
2023-01-31 | GSE218766 | GEO