Role of glucagon-like peptide-1 in the pathogenesis of experimental irritable bowel syndrome rat models

Abstract

Alterations in gut motility and visceral hypersensitivity are two major features of irritable bowel syndrome (IBS). The aim of this study was to investigate the roles of glucagon-like peptide-1 (GLP-1) in the pathogenesis of experimental IBS. Rat models of constipation-predominant IBS (IBS-C) and diarrhea-predominant IBS (IBS-D) were established. Fecal water content and behavioral responses to colorectal distention (CRD), using electromyography (EMG), were measured. The expression of glucagon-like peptide-1 receptor (GLP-1R) in the colon was detected by immunohistochemistry, and the serum concentration of GLP-1 was measured by ELISA assay. The movement of circular and longitudinal colonic muscle was detected using an organ bath recording technique. Compared to controls, the fecal water contents were lower in the IBS-C group, while they were higher in the IBS-D group (P<0.05). EMG response to CRD in the experimental IBS groups was increased compared with their respective controls (P<0.05). GLP-1R was localized in the mucosa layer, circular muscle and myenteric nerve plexus of the colon. Notably, the expression of GLP-1R in the IBS-C group was higher, but in the IBS-D group, it was lower compared with controls. The serum levels of GLP-1 in the IBS-C group were higher compared to those in the IBS-D group (P<0.05). In addition, administration of exogenous GLP-1 and exendin-4 inhibited colonic circular muscle contraction, particularly in the IBS-C group, while there was no significant effect on longitudinal muscle contraction. In conclusion, these results indicated that GLP-1 and GLP-1R are implicated in the pathogenesis of IBS-C and IBS-D.