Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; Laboratory Animal Centre, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. Electronic address: [Email]
OBJECTIVE : Similar to patients with Wolfram syndrome and to heterozygous Wolframin1 (Wfs1) mutation carriers, Wfs1-deficient mice exhibit impaired glucose tolerance and lower plasma insulin levels. Muscarinic receptor 3 agonists have previously been shown to potentiate glucose-stimulated insulin secretion. Therefore, the aim of this study was to investigate insulin-secretion dynamics in Wfs1-deficient mice and evaluate carbachol, muscarinic agonist and the ability to ameliorate the insulin secretion deficits caused by the Wfs1 mutation. METHODS : Wild-type Wfs1 heterozygous and Wfs1 mutant mice were used. Blood glucose was measured after glucose and carbachol administration. Insulin secretion was measured from serum using ELISA. RESULTS : Glucose administration causes hyperglycemia in Wfs1-deficient mice due to decreased insulin secretion. This deficit is abolished by administration of the muscarinic agonist carbachol. CONCLUSIONS : Activation of the muscarinic pathway to potentiate insulin secretion may present a target to manage diabetes resulting from Wfs1 deficiency.