PUBLICATION
Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment
- Authors
- Kimmel, R.A., Dobler, S., Schmitner, N., Walsen, T., Freudenblum, J., Meyer, D.
- ID
- ZDB-PUB-150919-1
- Date
- 2015
- Source
- Scientific Reports 5: 14241 (Journal)
- Registered Authors
- Kimmel, Robin, Meyer, Dirk, Schmitner, Nicole, Walsen, Tanja
- Keywords
- none
- MeSH Terms
-
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/genetics
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/pathology
- Mutation*
- Molecular Sequence Data
- Trans-Activators/chemistry
- Trans-Activators/genetics*
- Body Size
- Cell Survival/genetics
- Genotype
- Codon, Nonsense
- Sequence Alignment
- Homeodomain Proteins/chemistry
- Homeodomain Proteins/genetics*
- Disease Models, Animal
- Animals
- Animal Feed*
- Islets of Langerhans/drug effects
- Islets of Langerhans/metabolism
- Islets of Langerhans/pathology
- Hypoglycemic Agents/pharmacology*
- Amino Acid Sequence
- Animals, Genetically Modified
- Gene Knockout Techniques
- Insulin-Secreting Cells/drug effects
- Insulin-Secreting Cells/metabolism
- Animal Nutritional Physiological Phenomena*
- Glucose/metabolism
- Zebrafish
- PubMed
- 26384018 Full text @ Sci. Rep.
Citation
Kimmel, R.A., Dobler, S., Schmitner, N., Walsen, T., Freudenblum, J., Meyer, D. (2015) Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment. Scientific Reports. 5:14241.
Abstract
Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose. The hyperglycemia responds to pharmacologic anti-diabetic treatment and, as often seen in mammalian diabetes models, beta cells of pdx1 mutants show sensitivity to nutrient overload. This unique genetic model of diabetes provides a new tool for elucidating the mechanisms behind hyperglycemic pathologies and will allow the testing of novel therapeutic interventions in a model organism that is amenable to high-throughput approaches.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping