title: Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment.
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.
authors.affiliation: Institute of Molecular Biology/CMBI; Leopold-Francis University of Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Kimmel
authors.affiliation: Institute of Molecular Biology/CMBI; Leopold-Francis University of Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dobler
authors.affiliation: Institute of Molecular Biology/CMBI; Leopold-Francis University of Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitner
authors.affiliation: Institute of Molecular Biology/CMBI; Leopold-Francis University of Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
authors.forename: Tanja
authors.initials: T
authors.lastname: Walsen
authors.affiliation: Institute of Molecular Biology/CMBI; Leopold-Francis University of Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Freudenblum
authors.affiliation: Institute of Molecular Biology/CMBI; Leopold-Francis University of Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer
mesh_terms: D000595:Amino Acid Sequence; D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D030801:Animals, Genetically Modified; D049628:Body Size; D002470:Cell Survival / Q000235:genetics; D018389:Codon, Nonsense; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D015027:Zebrafish
chemical_list: D018389:Codon, Nonsense; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose