Behavioral Psychomotor Performance, Thyroid Functional and Structural Changes with Glucagon-Like Peptide-1 Receptor Agonists in Rats

Abstract

Background: Liraglutide, a glucagon-like peptide-1(GLP-1) receptor agonist, is used to treat patients with type-2 diabetes mellitus. It may have several adverse effects on thyroid glands as GLP-1 receptors are highly expressed in thyroid glands. Aim of Study: To investigate the effect of (liraglutide) on structure and function of thyroid gland in rats and its effect on behavioral and psychomotor function. Material and Methods: This study was carried out in the animal house, Faculty of Medicine, Suez Canal University. Rats were divided randomly into 3 groups, 6 rats/group. Control group: rats received normal saline once daily, GLP -short term and GLP -long term groups: rats received (0.075 mg/kg/day) liraglutide intraperitoneally (i.p.) once daily for 11 days and 12 weeks respectively. Anxiety was assessed using open field test and forced swimming test for depressive-like behavior. Estimation of TSH, FT3, FT4 and calcitonin in addition to histopathological and immunohistochemical changes for calcitonin expression in thyroid tissue as a clinical biomarker for C-cell diseases were done. Results: Anxiety-like behaviors were significantly increased in GLP -long term group. Forced swimming showed longer immobility time in the GLP -long term group. Reduced TSH, elevated calcitonin in GLP -long term group. FT4 and FT3 were insignificantly elevated. Histopathological changes were noticed and immunohistochemical expression of calcitonin significantly increased in thyroid tissue of GLP -long term group. Conclusion: There is a probable high risk of thyroid hyperplasia and cancer in GLP -long term treatment.