Investigation of the relationship of glp-1 with anxiety-like behaviour in streptozotocin induced diabetic rats

Introduction: Glucagon-like peptide-1 (GLP-1) is an incretin that is secreted mostly in the terminal ileum and increases glucose-induced insulin synthesis while decreasing glucagon secretion. GLP-1 is inactivated by the dipeptidyl-peptidase 4 (DPP-4) enzyme in the plasma. The effect of GLP-1 on anxiety is unclear. It is well-known that anxiety is more common in diabetics. Aim: The aim of this study was to investigate the relationship of GLP-1 with anxiety-like behavior in diabetic rats. Method: Female Wistar Albino rats were divided into four groups; (1) Sitagliptin (DPP-4 enzyme inhibitor), (2) Diabetes+sitagliptin, (3) Diabetes, (4) Control. Diabetes was induced by streptozotocin (single 40mg/kg, intraperitoneally). After forty eight hours rats with blood glucose levels higher than 250mg/dL were considered as diabetic. Sitagliptin was given 20mg/kg orally for 21 days. Anxiety levels were evaluated with open field and elevated plus maze tests. GLP-1 and GLP-1 receptor levels in ileum, prefrontal cortex tissues and plasma were evaluated with ELISA and immunohistologic examination. Results: In non-diabetic rats, sitagliptin increased anxiety levels, decreased plasma GLP-1 levels as well as both GLP-1 and GLP-1 receptor levels in prefrontal cortex (p<0.05). Also, there was a strong positive correlation between anxiety and prefrontal cortex GLP-1 receptor levels (r=0.63, p<0.01). Diabetic rats exhibited greater anxiety-like behavior in the elevated plus maze test (p<0.05). GLP-1 receptor levels in prefrontal cortex were decreased in diabetic rats (p<0.05). Both GLP-1 and GLP-1 receptor levels in ileum were decreased in diabetic rats (p<0.05). Sitagliptin use in diabetics didn't affect anxiety-like behavior or change ileum and prefrontal cortex GLP-1 receptor levels; but decreased ileum GLP-1 levels (p<0.05). Conclusion: GLP-1 created anxiety-like behavior in healthy rats as correlated with the prefrontal cortex GLP-1 levels; but didn't affect prefrontal cortex GLP-1 levels or anxiety-like behaviour in diabetic rats. Key Words: GLP-1, anxiety-like behaviour, diabetes, sitagliptin