PUBLICATION
GLUT12 deficiency during early development results in heart failure and a diabetic phenotype
- Authors
- Jiménez-Amilburu, V., Jong-Raadsen, S., Bakkers, J., Spaink, H.P., Marín-Juez, R.
- ID
- ZDB-PUB-141019-1
- Date
- 2015
- Source
- The Journal of endocrinology 224(1): 1-15 (Journal)
- Registered Authors
- Bakkers, Jeroen, Marín-Juez, Rubén, Spaink, Herman P.
- Keywords
- none
- Datasets
- GEO:GSE59683
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/embryology
- Diabetes Mellitus, Type 2/genetics*
- Diabetic Cardiomyopathies/complications
- Diabetic Cardiomyopathies/embryology
- Diabetic Cardiomyopathies/genetics*
- Disease Models, Animal*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/drug effects
- Glucose Transport Proteins, Facilitative/deficiency
- Glucose Transport Proteins, Facilitative/genetics*
- Heart Failure/genetics*
- Heart Failure/pathology
- Insulin/pharmacology
- Metformin/pharmacology
- Phenotype
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics*
- PubMed
- 25326603 Full text @ J. Endocrinol.
Citation
Jiménez-Amilburu, V., Jong-Raadsen, S., Bakkers, J., Spaink, H.P., Marín-Juez, R. (2015) GLUT12 deficiency during early development results in heart failure and a diabetic phenotype. The Journal of endocrinology. 224(1):1-15.
Abstract
Cardiomyopathies-associated metabolic pathologies (e.g. T2D and insulin resistance) are a leading cause of mortality. It is known that the association between the pathologies works in both directions, where heart failure can lead to metabolic derangements such as insulin resistance. This intricate crosstalk exemplifies the importance of a fine coordination between one of the most energy demanding organs and an equilibrated carbohydrate metabolism. In this light, to assist in the understanding of the role of insulin regulated glucose transporters and the development of cardiomyopathies, we have developed a model for glut12 deficiency in zebrafish. GLUT12 is a novel insulin-regulated glucose transporter expressed in the main insulin sensitive tissues such as cardiac and skeletal muscle and adipose tissue. Here we show that glut12 knockdown impacts the development of the embryonic heart resulting in abnormal valve formation. Moreover, glut12 deficient embryos also exhibited poor glycemic control. Glucose measurements showed that these larvae were hyperglycemic and resistant to insulin administration. Transcriptome analysis demonstrated that a number of genes known to be important in cardiac development and function as well as metabolic mediators were dysregulated in these larvae. These results indicate that glut12 is an essential glucose transporter in the heart where the reduction of glucose uptake due to glut12 deficiency leads to heart failure presumably due to the lack of glucose as energy substrate. In addition, the diabetic phenotype displayed by these larvae after glut12 abrogation highlights the importance of this glucose transporter during early developmental stages.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping