Muscarinic Agonist Ameliorates Insulin Secretion in Wfs1-Deficient Mice

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.

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.

Glucose administration causes hyperglycemia in Wfs1-deficient mice due to decreased insulin secretion. This deficit is abolished by administration of the muscarinic agonist carbachol.

Activation of the muscarinic pathway to potentiate insulin secretion may present a target to manage diabetes resulting from Wfs1 deficiency.