title: Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1.
abstract: Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes.
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Sedman
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Kertu
authors.initials: K
authors.lastname: Rünkorg
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Maarja
authors.initials: M
authors.lastname: Krass
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luuk
authors.affiliation: Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Mario
authors.initials: M
authors.lastname: Plaas
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Centre for Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia; Tartu University Hospital, 8 L. Puusepa Street, 51014 Tartu, Estonia.
authors.forename: Vallo
authors.initials: V
authors.lastname: Volke
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D000077270:Exenatide; D020022:Genetic Predisposition to Disease; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000494:pharmacology*; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology*; D014929:Wolfram Syndrome / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D008565:Membrane Proteins; D010455:Peptides; D014688:Venoms; C114987:wolframin protein; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists