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The increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes.

Krass M, Rünkorg K, Vasar E, Volke V. Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice. Objective:The aim of this study was to compare the behavioural and hormonal effects of systemic (subcutaneous) treatment with glucaemically equipotent doses of exenatide and liraglutide in mice. Methods: The effects of glucagon-like peptide-1 (GLP-1) receptor agonists were determined on anxiety level in the light-dark compartment test, the motor activity in automated activity cages and finally the forced swimming test was performed. Results: Both exenatide (1-20 μg/kg) and liraglutide (200-1200 μg/kg) decreased the glucose levels up to 30% in freely fed animals. In glucaemically equipotent doses the drugs induced very similar behavioural and hormonal effects: there was no change on anxiety level or immobility time, however, both drugs suppressed motor activity and increased corticosterone levels. Conclusion: We conclude that the two clinically approved GLP-1 receptor agonists induce very similar suppression of motor activity and stimulation of corticosterone release in mice. Significant outcomes• Glucagon-like peptide-1 (GLP-1) agonists are neutral in tests of anxiety and depression after acute administration. • Both exenatide and liraglutide stimulate corticosterone release after acute administration. Limitations• In clinical context, the chronic effects of GLP-1 agonists are more important and should be addressed in future studies.