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.
Early chronic intervention with the GLP-1 receptor agonist liraglutide starting before the onset of metabolic symptoms prevented the development of glucose intolerance, improved insulin and glucagon secretion control, reduced ER stress and inflammation in Langerhans islets in Wfs1 mutant rats.
These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age.