Danio rerio
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA255949 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Diabetic cardiomyopathy, an increasingly global epidemic and a major cause of heart failure with preserved ejection fraction (HFpEF), is associated with hyperglycemia, insulin resistance, and intra-cardiomyocyte calcium mishandling. Here we identify that, in db/db mice with type 2 diabetes induced HFpEF, abnormal remodeling of cardiomyocyte transverse-tubule microdomains occurs with downregulation of the membrane scaffolding protein cardiac bridging integrator 1 (cBIN1). Transduction of cBIN1 by AAV9 gene therapy can restore transverse-tubule microdomains to normalize intracellular distribution of calcium handling proteins and, surprisingly, glucose transporter 4 (GLUT4). Cardiac proteomics revealed that AAV9-cBIN1 normalizes components of calcium handling and GLUT4 translocation machineries. Functional studies further identified that AAV9-cBIN1 normalizes insulin-dependent glucose uptake in diabetic cardiomyocytes. Phenotypically, AAV9-cBIN1 rescues cardiac lusitropy, improves exercise intolerance, and ameliorates hyperglycemia in diabetic mice. Restoration of transverse-tubule microdomains can improve cardiac function in the setting of diabetic cardiomyopathy, and also improve systemic glycemic control.
2023-10-24 | PXD044236 | Pride
Project description:The zebrafish runzel mutant results in a novel muscular dystrophy phenotype due to a titin mutation
| PRJNA94433 | ENA
Project description:Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients, but its pathogenesis remains unclear. Sodium glucose cotransporter 2 inhibitors (SGLT2i) can effectively reduce the risk of cardiovascular death and heart failure in DCM patients, but the underlying mechanism has not been elucidated. We established a DCM rat model followed by treatment with empagliflozin (EMPA) for 12 weeks. The proteomics of the myocardium in the rat model was performed to identify the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i.
2023-03-10 | PXD036090 | Pride
Project description:Assessment of hematopoietic failure due to RPL11 deficiency in a zebrafish model of Diamond–Blackfan anemia by deep sequencing
| PRJNA222400 | ENA
Project description:Deficiency in class III PI3-kinase induces intestinal epithelial damage and inflammatory bowel disease like phenotype in zebrafish
| PRJNA396243 | ENA
Project description:Cardiac glucose delivery and utilization are reduced in diabetes despite hyperglycemia. Mitochondrial dysfunction contributes to heart failure in diabetic patients. The loss of mitochondrial substrate flexibility in regulating cellular and cardiac function is actively under investigation.
2020-10-05 | GSE123975 | GEO
Project description:Diabetes is a disorder characterized by loss of beta cell mass and/or beta cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell derived-beta cells faithfully reflect the phenotypes of a diabetic subject, we generated induced pluripotent stem cells from diabetic subjects (MODY2) with heterozygous loss-of-function of the gene encoding glucokinase (GCK). These stem cells differentiated into beta cells with an efficiency comparable to controls, and expressed markers of mature beta cells, urocotin-3 and zinc transporter 8 upon transplantation into mice. While insulin secretion in response to arginine or other secretagogues was identical to cells from healthy controls, GCK mutant beta cells required higher glucose levels to stimulate insulin secretion. Importantly this glucose-specific phenotype was fully reverted upon gene sequence correction by homologous recombination. Our results demonstrate that stem cell-derived beta cells reflect beta cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on beta cell function.
2013-04-05 | GSE45777 | GEO
Project description:Diabetic cardiomyopathy (DbCM) occurs independently of cardiovascular diseases or hypertension, often leading to heart failure and death. To elucidate the molecular mechanisms involved in the DbCM progress, we performed quantitative proteomic profiling analysis in the left ventricle (LV) of leptin receptor‐deficient mice. Six‐month‐old C57BL/6Jlepr/ lepr (db/db) mice exhibited a phenotype of DbCM. By quantitative shotgun proteomic analysis, we identified 53 differentially expressed proteins in db/db mice, mainly associated with energy metabolism. The subunits of ATP synthase that form the F1 domain and Cytochrome c1, a catalytic core subunit of the complex III that is responsible for electron transfer to Cytochrome c, were upregulated in diabetic LVs. Upregulation of these key proteins may represent an adaptive mechanism by the diabetic heart resulting in increased electron transfer and thereby enhancement of mitochondrial ATP production. Conversely, diabetic LVs also showed a decrease in peptide levels of NADH dehydrogenase 1 beta subcomplex subunit 11, a subunit of complex I that catalyzes the transfer of electrons to ubiquinone. Moreover, an atypical kinase COQ8A, an essential lipid‐soluble electron transporter involved in the biosynthesis of ubiquinone, was also downregulated in diabetic LVs. Our study indicates that despite attempts by hearts from the diabetic mice to augment mitochondrial ATP production, decreased levels of key components of the electron transport chain may contribute to impaired mitochondrial ATP production.
2021-12-02 | PXD029566 | Pride