Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment

Sci Rep. 2015 Sep 18;5:14241. doi: 10.1038/srep14241.

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.

Publication types

  • Research Support, Non-U.S. Gov't

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

Substances

  • Codon, Nonsense
  • Homeodomain Proteins
  • Hypoglycemic Agents
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Glucose