The GLP-1R agonist semaglutide reshapes pancreatic cancer associated fibroblasts reducing collagen hydroxyprolination and favoring immune infiltration.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1108693 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28955873_1.fastq.gz | Fastqsanger.gz | |||
| SRR28955873_2.fastq.gz | Fastqsanger.gz | |||
| SRR28955874_1.fastq.gz | Fastqsanger.gz | |||
| SRR28955874_2.fastq.gz | Fastqsanger.gz | |||
| SRR28955875_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:Gut intraepithelial lymphocytes (IELs) are one of the few immune cell populations in the body that expresses glucagon-like 1 receptors (GLP-1R). To test the potential effects of GLP-1 on the gut microbiota through the gut IEL GLP-1R, we performed 16s rRNA seq on the DNA isolated from the fecal pellet of Lck-Cre; Glp1rfl/fl mice (Glp1rTcell-/-) or controls (Glp1rTcell+/+) fed a high-fat diet (HFD) for 12 weeks followed by 1 week of HFD plus semaglutide (10 ug/kg) or vehicle treatment. Fecal pellets from a group of age-matched, sex-matched control mice were included as a chow control group.
2022-08-29 | GSE202452 | GEO
Project description:Metabolic syndrome represents a risk factor of pancreatic ductal adenocarcinoma (PDAC), the gastrointestinal cancer with the lowest survival rate and therapeutic outcome. PDAC results bidirectional interconnected with metabolic alteration, which favors its onset and occurs during early phases of its development. Pancreatic neoplastic lesions evolve within a highly dense desmoplastic stroma, characterized by abundant extracellular matrix deposition consequence of a prominent cancer associated fibroblast (CAF) activation. Here, the complex association between dysmetabolism and PDAC has been analyzed with a specific focus on CAFs to unveil novel targets exploitable for diagnostic and therapeutic purposes. Methods: PDAC development upon dysmetabolic conditions was investigated in: 1) wild type immunocompetent syngeneic mice by orthotopic transplantation of PanIN-bearing Pdx1-Cre; Kras+/LSL-G12D; Trp53+/LSL-R172H organoids (KPC mice) fed with high fat diet to recapitulate dysmetabolism-dependent alterations; and 2) primary pancreatic CAFs isolated from chemotherapy naïve PDAC patients with or without an history of metabolic syndrome. Results: The dysmetabolic-associated higher PDAC aggressiveness was paralleled by an enrichment of collagen fibrils due to an increased function of the prolyl 4-hydroxylase subunit alpha 1 (P4HA1). Upon dysmetabolic conditions, P4HA1 boosts collagen hydroxy-prolination, intensifying collagen contraction strength and thus preventing CD3 positive lymphocyte PDAC infiltration. Interestingly, semaglutide, an incretin agonist with anti-diabetic and anti-obesity properties, is able to prevent the higher stromal deposition of PDAC observed in dysmetabolic conditions, preventing CAF contraction, allowing immune infiltration and reducing tumor development. Conclusion: These results shed light on novel therapeutic options for PDAC patients affected by metabolic syndrome aimed at pancreatic cancer stroma reshape
2025-01-29 | GSE266899 | GEO
Project description:To gain insight into the biological functions of the highly expressed GLP-1R in Brunnerâs glands, transcriptome analyses were conducted in male GLP-1R-/- and wild-type control mice. Analyses were performed 6 hours after a single s.c. dose of exendin-4 (1.0mg/kg s.c.), following 18 hours of two doses of exendin-4 (1.0 mg/kg s.c., administered at 0 and 9 hours), and in untreated controls. Brunnerâs glands were isolated by laser capture micro dissection and extracted total RNA was used for microarray profiling. A total of 18 samples consisting of laser captured microdissected Brunner's glands from individual male GLP-1R-/- and wild-type (CD-1) mice. Before the isolation of Brunner's glands, mice were dosed with exendin-4 for 6 and 18 hours. The extracted total RNA from Brunner's glands were compared by full transcriptome profiling.
2016-07-01 | E-GEOD-80119 | biostudies-arrayexpress
Project description:Early drivers of Type 2 diabetes mellitus (T2D) include ectopic fat accumulation, especially in the liver, that significantly impairs insulin sensitivity. In a T2D setting, GLP-1R/GCGR dual agonists have been shown to reduce glycaemia, body weight and hepatic steatosis. We utilized cotadutide, a well characterized GLP-1R/GCGR dual-agonist, to demonstrate improved insulin sensitivity during hyperinsulinemic euglycemic clamp following sub-chronic dosing in male, diet-induced obese mice. Phosphoproteomic analyses of insulin stimulated liver from cotadutide treated diet-induced obese (DIO) mice identified novel phosphorylation sites on key insulin signalling pathway proteins associated with improved insulin sensitivity. Cotadutide or GCGR monoagonist treatment also resulted in specific increased brown adipose tissue (BAT) insulin-stimulated glucose uptake, while GLP-1R monoagonist only showed a weak effect. BAT from cotadutide treated mice had induction of UCP-1 protein, increased mitochondrial area and a transcriptomic profile of increased fat oxidation and mitochondrial activity. Finally, the cotadutide-induced improvement in insulin sensitivity was associated with reduced insulin secretion from isolated pancreatic islet β-cells indicating reduced insulin secretory demand. Thus, GLP-1R/GCGR dual agonism provides multimodal efficacy to decrease hepatic steatosis and consequently improve insulin sensitivity, in concert with recovery of endogenous β-cell function and reduced insulin demand. This substantiates GLP-1R/GCGR dual-agonism as a novel and effective T2D treatment
2025-03-28 | PXD057744 | Pride
Project description:In this study, we compared the treatment with one of 2 GLP-1 receptor agonists, Liraglutide and Semaglutide on the gene expression in 6 different DIO rat brain areas known to express the GLP-1 receptor. DIO rats were treated with vehicle, liraglutide, semaglutide or weight-matched for 23 days and tissue from the brain areas LS, PVH, ARH, DMH, AP and NTS was obtained with LCM.
2020-03-26 | E-MTAB-8078 | biostudies-arrayexpress
Project description:To gain insight into the biological functions of the highly expressed GLP-1R in Brunner’s glands, transcriptome analyses were conducted in male GLP-1R-/- and wild-type control mice. Analyses were performed 6 hours after a single s.c. dose of exendin-4 (1.0mg/kg s.c.), following 18 hours of two doses of exendin-4 (1.0 mg/kg s.c., administered at 0 and 9 hours), and in untreated controls. Brunner’s glands were isolated by laser capture micro dissection and extracted total RNA was used for microarray profiling.
2016-07-01 | GSE80119 | GEO
Project description:Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to impact glucose homeostasis and, more recently, the somatotropic axis. While the effects of GLP-1RAs have been extensively studied in the context of diet-induced obesity, their impact on physiology in other nutritional contexts have been less explored. We investigated the potential beneficial effects of the GLP-1RA semaglutide during juvenile protein malnutrition, a dietary challenge known to cause stunted growth and to disrupt metabolic homeostasis. We used a murine model to assess the effects of twice-weekly subcutaneous injections of semaglutide during juvenile protein malnutrition. Glucose metabolism was evaluated through in vivo oral glucose tolerance test, ex vivo glucose-stimulated insulin secretion in isolated pancreatic islets and histology of the pancreas. We combined linear growth monitoring, analysis of the growth hormone/insulin-like growth factor 1 signaling pathway and liver bulk RNA sequencing to characterize the effects of semaglutide on the somatotropic axis during juvenile protein malnutrition. Semaglutide improved glucose tolerance in control and malnourished mice, but differentially impacted pancreatic islet physiology depending on the dietary protein intake. While semaglutide did not alter growth in control conditions, it further inhibited growth of malnourished mice associated with reduction in fat but not lean mass. Surprisingly, semaglutide had no discernible effect on the functionality of the somatotropic axis in malnourished mice. Liver transcriptomics revealed that semaglutide could interfere with the growth of malnourished juvenile mice by altering circadian rhythm and thermogenesis. Our data reveal that semaglutide interacts differentially with the physiology of juvenile mice depending on their dietary protein intake. We found that semaglutide influences glucose metabolism and linear growth in a diet-dependent manner, underscoring the importance of examining the effects of GLP-1RAs across various nutritional contexts and developmental stages.
2024-05-07 | GSE266477 | GEO
Project description:Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide 1 receptor (GLP-1R) are expressed in the central nervous system (CNS) and regulate food intake. Here, we demonstrate that a peptide-antibody conjugate that blocks GIPR while simultaneously activating GLP-1R (GIPR-Ab/GLP-1) requires both CNS GIPR and CNS GLP-1R for additive effects on body weight loss in obese, primarily male, mice. Moreover, dulaglutide produces greater weight loss in CNS GIPR KO mice compared to WT mice, and the extent of weight loss achieved with dulaglutide + GIPR-Ab is attenuated in CNS GIPR KO mice. WT mice treated with GIPR-Ab/GLP-1 or CNS GIPR KO mice exhibit similar changes in gene expression related to tissue remodeling, lipid metabolism, and inflammation in white adipose tissue and liver. Moreover, GIPR-Ab/GLP-1 is detected in circumventricular organs in the brain and activates c-FOS in downstream neural substrates involved in appetite regulation. Hence, both CNS GIPR and GLP-1R signaling are required for the full effect of a GIPR-Ab/GLP-1 peptide-antibody conjugate, with loss of CNS GIPR activity potentiating the actions of GLP-1R agonism.
2025-04-29 | GSE293291 | GEO
Project description:Glucagon and glucagon-like peptide-1 (GLP-1) are hormones involved in energy homeostasis. GLP-1 receptor (GLP-1R) agonism reduces food intake and delays gastric emptying, and glucagon receptor (GCGR) agonism increases energy expenditure by thermogenesis. BI 456906 is a subcutaneous, once-weekly injectable dual GLP-1R/GCGR agonist in development for the treatment of obesity or non-alcoholic steatohepatitis. Here we show that BI 456906 is a potent dual agonist with an extended half-life in human plasma. Key GLP-1R-mediated mechanisms of reduced food intake, delayed gastric emptying and improved glucose tolerance were confirmed in GLP-1R knockout mice. GCGR activity was confirmed by reduced plasma amino acids, increased hepatic expression of nicotinamide N-methyltransferase and increased energy expenditure. BI 456906 produced greater bodyweight reductions than maximally efficacious semaglutide doses and modulated gene expression, including genes involved in amino acid metabolism. BI 456906 is a potent dual agonist that produces bodyweight-lowering effects through both GLP-1R and GCGR agonism.
2022-12-09 | GSE211105 | GEO
Project description:Obesity, a complex ailment, has demonstrated promising weight reduction outcomes with glucagon-like peptide-1 receptor agonists (GLP-1RA) drugs like semaglutide. Nevertheless, their intricate mechanisms remain elusive. In this study, we constructed single-cell transcriptomic profiles of intestinal epithelium from individuals with normal and high BMI, revealing significant transcriptomic and metabolic alterations.
2025-03-03 | GSE261178 | GEO