Objectives: 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.
Keywords: Wolframin1 (Wfs1); diabetes; diabète; hyperglycemia; hyperglycémie; insulin secretion; muscarinic receptor M3; récepteur muscarinique de sous-type M3 (récepteur M3); sécrétion d'insuline; wolframine 1 (WFS1).
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