Insulin fused to apolipoprotein A-I
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA671860 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In order to evaluate the in vivo properties of insulin fused to apolipoprotein A-I, we compared the pharmacodynamic properties in the liver to other insulin derivatives with long half-life in circulation: the fusion protein of albumin and insulin (Albulin) [30]. We administered subcutaneously saline, Albulin or Insulin-Apo to wild type mice, and 6 hours later, livers were extracted and homogenized. RNA was obtained and used to analyze the gene expression profile induced by the different insulin modifications.
2020-10-27 | GSE160105 | GEO
Project description:We sought to explore the relationship between apolipoprotein AV (APOAV) overexpression and insulin resistance in hepatocytes. The insulin-resistant HepG2 cell model was constructed and then APOAV overexpressed HepG2 cells (B-M) were induced by infecting with recombinant adenovirus vector. Microarray data were developed from B-M samples compared with negative controls (A-con) and the microarray data were analyzed by bioinformatic methods. APOAV overexpression induced 313 up-regulated genes and 563 down-regulated ones in B-M sample. The differentially expressed genes (DEGs) were significantly classified in Fat digestion and absorption pathway. Protein-protein interaction network was constructed and AGTR1 (angiotensin II receptor type 1) and P2RY2 (purinergic receptor P2Y, G-protein coupled 2) were found to be the significant nodes closely related with G-protein related signaling. Additionally, overexpression of APOAV could change the expression of Glut4 and release insulin resistance of hepatic cells. Thus, APOAV overexpression may prevent the insulin resistance in liver cells by mediating the genes such as AGTR1 and P2RY2.
2020-07-09 | GSE134062 | GEO
Project description:Next Generation Sequencing explore the relationship between apolipoprotein AV (APOAV) overexpression and insulin resistance in hepatocytes.
| PRJNA553668 | ENA
Project description:The anti-diabetic drug and agonist of the peroxisome proliferator-activated receptor gamma (Pparg), rosiglitazone, was recently withdrawn in many countries because the drug use was associated with an increased risk of heart failure. To investigate underlying pathomechanisms, we chose 6-month-old apolipoprotein E (apoE)-deficient mice, which are prone to atherosclerosis and insulin resistance, and thereby mimic the risk profile of patients with cardiovascular disease. After 8 weeks of rosiglitazone treatment (30 mg/kg/day), echocardiography and histology analyses demonstrated that rosiglitazone had induced heart failure with cardiac dilation. Concomitantly, cardiac lipid overload and lipid-induced cardiomyocyte death developed. The microarray gene expression study of heart tissue from rosiglitazone-treated apoE-deficient mice relative to untreated apoE-deficient mice and non-transgenic B6 mice identified cardiac Pparg-dependent lipid metabolism genes in rosiglitazone-treated mice, which seem to trigger a major heart failure promoting pathway. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) rosiglitazone-treated 8-month-old apolipoprotein (apoE)-deficient mice with symptoms of heart failure, (ii) untreated 8-month-old apoE-deficient mice, and (iii) age-matched, untreated, non-transgenic B6 control mice.
2011-03-18 | E-GEOD-28031 | biostudies-arrayexpress
Project description:Background: Targeting long-lasting insulins to the liver may improve metabolic alterations that are not corrected with current insulin replacement therapies. However, insulin is only able to promote lipogenesis but not to block gluconeogenesis in the insulin-resistant liver, exacerbating liver steatosis associated with diabetes. Methods: In order to overcome this limitation, we fused a single-chain insulin to apolipoprotein A-I, and we evaluated the pharmacokinetics and pharmacodynamics of this novel fusion protein in wild type mice and in db/db mice using both recombinant proteins and recombinant adenoassociated virus (AAV). Results: Here, we report that the fusion protein between single-chain insulin and apolipoprotein A-I prolonged the insulin half-life in circulation, and accumulated in the liver. We analyzed the long-term effect of these insulin fused to apolipoprotein A-I or insulin fused to albumin using AAVs in the db/db mouse model of diabetes, obesity, and liver steatosis. While AAV encoding insulin fused to albumin exacerbated liver steatosis in several mice, AAV encoding insulin fused to apolipoprotein A-I reduced liver steatosis. These results were confirmed upon daily subcutaneous administration of the recombinant insulin-apolipoprotein A-I fusion protein for six weeks. The reduced liver steatosis was associated with reduced body weight in mice treated with insulin fused to apolipoprotein A-I. Recombinant apolipoprotein A-I alone significantly reduces body weight and liver weight, indicating that the apolipoprotein A-I moiety is the main driver of these effects. Conclusion: The fusion protein of insulin and apolipoprotein A-I could be a promising insulin derivative for the treatment of diabetic patients with associated fatty liver disease.
| S-EPMC7934061 | biostudies-literature
Project description:Transient GFP-fused DARPin expression effects on transcription
| PRJEB51294 | ENA
Project description:Assaying gene expression in sutural bone fragments from patients diagnosed with non-syndromic craniosynostosis. Sutural fragments were collected from both the fused and patent cranial suture of infants during cranial vault reconstruction. Gene expression was compared between the patent and fused sutures using the paired t-test. The aim was to identify thoses genes significantly differentially expressed in fused suture relative to patent.
2013-09-12 | GSE50796 | GEO
Project description:Assaying gene expression in sutural bone fragments from patients diagnosed with non-syndromic craniosynostosis. Sutural fragments were collected from both the fused and patent cranial suture of infants during cranial vault reconstruction. Gene expression was compared between the patent and fused sutures using the paired t-test. The aim was to identify thoses genes significantly differentially expressed in fused suture relative to patent. Total RNA isolated from patent and fused human cranial sutures was assayed. Expression in synostosed suture was compared to patent suture.
2013-09-12 | E-GEOD-50796 | biostudies-arrayexpress
Project description:Despite a high degree of homology, insulin and IGF-1 receptors (IR/IGF1R) mediate distinct cellular and physiological functions. Here, using chimeric and site-mutated receptors, we demonstrate how domain differences between IR and IGF1R contribute the distinct functions of these receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to its higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. We generated mouse brown preadipocytes in which both insulin and IGF-1 receptors (IR and IGF1R) had been genetically inactivated using Cre-lox recombination. These IR and IGF1R DKO cells were then reconstituted with wild-type mouse IR, IGF1R, or one of two chimeric receptors: IR/IGF1R with the IR extracellular domain (ECD) fused to the IGF1R transmembrane and intracellular domains (ICD) and IGF1R/IR with the ECD of IGF1R fused to the ICD domains of IR. Three independent clones for each line were used for the study. For expression analysis, we serum-starved the preadipocytes clones overnight and stimulated cells with 100 nM insulin, IGF-1 or vehicle for 6 h, and subjected the cellular RNA to analysis using Affymetrix Mouse Gene 2.0 ST arrays.
2016-07-01 | E-GEOD-81921 | biostudies-arrayexpress
Project description:insulin resistant duodenum vs. non-insulin resistant duodenum
| PRJNA615363 | ENA