Preventive treatment with liraglutide protects against development of glucose intolerance in a rat model of Wolfram syndrome

Sci Rep. 2018 Jul 5;8(1):10183. doi: 10.1038/s41598-018-28314-z.


Wolfram syndrome (WS) is a rare autosomal recessive disorder caused by mutations in the WFS1 (Wolframin1) gene. The syndrome first manifests as diabetes mellitus, followed by optic nerve atrophy, deafness, and neurodegeneration. The underlying mechanism is believed to be a dysregulation of endoplasmic reticulum (ER) stress response, which ultimately leads to cellular death. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been shown to normalize ER stress response in several in vitro and in vivo models. 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. Thus, treatment with GLP-1 receptor agonists might be a promising strategy as a preventive treatment for human WS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Calmodulin-Binding Proteins / genetics
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects
  • Gene Knockout Techniques
  • Glucagon / metabolism
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucose Intolerance / blood
  • Glucose Intolerance / diagnosis
  • Glucose Intolerance / etiology
  • Glucose Intolerance / prevention & control*
  • Glucose Tolerance Test
  • Humans
  • Incretins / administration & dosage*
  • Injections, Subcutaneous
  • Insulin / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Liraglutide / administration & dosage*
  • Male
  • Membrane Proteins / genetics
  • Rats
  • Rats, Transgenic
  • Treatment Outcome
  • Wolfram Syndrome / complications*
  • Wolfram Syndrome / genetics


  • Blood Glucose
  • Calmodulin-Binding Proteins
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Insulin
  • Membrane Proteins
  • WFS1 protein, rat
  • Liraglutide
  • Glucagon