ZFIN ID: ZDB-PUB-150919-1
Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment
Kimmel, R.A., Dobler, S., Schmitner, N., Walsen, T., Freudenblum, J., Meyer, D.
Date: 2015
Source: Scientific Reports   5: 14241 (Journal)
Registered Authors: Kimmel, Robin, Meyer, Dirk, Schmitner, Nicole, Walsen, Tanja
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animal Feed*
  • Animal Nutritional Physiological Phenomena*
  • Animals
  • Animals, Genetically Modified
  • Body Size
  • Cell Survival/genetics
  • Codon, Nonsense
  • Diabetes Mellitus, Type 2/drug therapy
  • Diabetes Mellitus, Type 2/genetics
  • Diabetes Mellitus, Type 2/metabolism
  • Diabetes Mellitus, Type 2/pathology
  • Disease Models, Animal
  • Gene Knockout Techniques
  • Genotype
  • Glucose/metabolism
  • Homeodomain Proteins/chemistry
  • Homeodomain Proteins/genetics*
  • Hypoglycemic Agents/pharmacology*
  • Insulin-Secreting Cells/drug effects
  • Insulin-Secreting Cells/metabolism
  • Islets of Langerhans/drug effects
  • Islets of Langerhans/metabolism
  • Islets of Langerhans/pathology
  • Molecular Sequence Data
  • Mutation*
  • Sequence Alignment
  • Trans-Activators/chemistry
  • Trans-Activators/genetics*
  • Zebrafish
PubMed: 26384018 Full text @ Sci. Rep.
FIGURES
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.
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