1.effect Of GLP-1 And GLP-1 Receptor On The Pathogenetic Mechanism Of Irritable Bowel Syndrome Subgroups In Rat Models 2.The Distribution Of Mitochondrial Uncoupling Protein 2 (UCP2) In Intestinal Tract And Its Effect On Secretion Of GLP-1

Background:Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by the abdominal pain or discomfort with altered bowel habits. However, the pathgenetic mechanism of IBS is still not completely understood. Nowedays, Visceral hyperalgesia and the abnormality of the gastrointestinal motility assumed to be the main factors. Glucagon-like peptide-1 (GLP-1) (7-36) amide is secreted from the L cells in the gut after a meal and is well known for its action on theβcell, resulting in enhanced insulin secretion and inhibit glucagon secretion, this is the so-called incretion effect. (GLP-1)(7-36) amide exerts its biological actions via highly specific G-protein-coupled receptors. GLP-1 receptor expressed in the gastrointestinal tract, pancreatic gland and the central nervous system. (GLP-1)(7-36) amide profoundly affects the motor function of the gastrointestinal tract by inhibiting gastric emptying and small bowel motility in healthy volunteer and patients with irritable bowel syndrome (IBS). Meanwhile, GLP-1 analogues have the effect in terms of total pain relief response in patients affected by acute pain attacks due to IBS, especially those who had postprandial abdominal pain. However, the action mechanism of pain-relieving effect of GLP-1 analogue is still not understood. There is rare document about the effects of GLP-1 and its receptor on the pathogenic mechanism of IBS rat models. Aim:To investigate the effect of change in GLP-1 and GLP-1 receptor on the pathogenetic mechanism of irritable bowel syndrome (IBS) subgroups in rat models. Methods:1. Forty-eight SD rats were divided into C-IBS group, D-IBS group, and the blank control group.2. The D-IBS model was created in rats by intracolonic instillation of acetic acid and by restraint stress. The C-IBS model was created in rats by gastric instillation of 0-4℃cool water daily for 14 days. A blank control group was also made.3. Weight of the feces and moisture capacity of the feces were calculated. Viscerosomatic sensitivity was assessed with electromyography (EMG). The charcoal suspension gastric instillation experiment was used to detect the intestinal transit. Histological analysis of colonic tissue was performed.4. The distributions of GLP-1 R in colon tissue were detected by immunohistochemistry. The amount of active GLP-1 in serum was detected by ELISA.Levels of GLP-1 R mRNA and protein in colon tissues was examined.Results:1. Compared with control group,wet weight ,water content of the feces and intestinal transit rate decreased obviously in the C-IBS group (P < 0.05), while the D-IBS group increased significantly (P < 0.05).2. Compared with control group, amplitude of the abdominal muscle contraction at the pressure of 20mmHg, 40mmHg and 60mmHg were higher.Meanwhile, D-IBS group was higher than the C-IBS group (P < 0.05)3. The expressions of GLP-1 R mRNA and protein in C-IBS group were higher than those in control group (P < 0.05). A Lower leval was observed in the D-IBS group (P < 0.05).4. GLP-1 R mainly localized in the colon mucosa, circular muscle and myenteric nerve plexus.Leval of the GLP-1 in serum in C-IBS group was higer than D-IBS group (P < 0.05).Conclusions: 1. The changes of GLP-1 in serum and GLP-1 R in the colon are related to IBS subgroups, visceral sensitivity and colonic motility dysfunction.2. GLP-1 and GLP-1 R play a role in the pathgenetic mechanism of IBS subgroup. Background:Mitochondrial uncoupling protein 2 (uncoupling protein2, UCP2) is a member of the family of mitochondrial uncoupling proteins. UCP2mRNA expression in the digestive tract is a lot, the physiological function of UCP2 is not yet entirely clear.The existing research suggests that UCP2 has a role in regulation of mitochondrial ATP generation. Some literatures reported that UCP2 decreased ATP / ADP ratio;UCP2 has a role in negative regulation of insulin secretion.The digestive tract is the largest endocrine system. Gastrointestinal peptides play an important role in the maintenance of glucose homeostasis in vivo. Glucagon-like peptide -1 (glucagon-like peptide 1, GLP-1) is derived from the intestinal L cells,it is an important regulator of insulin secretion .The existing studies showed that intestinal L cells are glucose-sensitive cells, and also have the same ATP-sensitive K + channels asβcells, these ion channels had SUR1 and Kir6.2 two subunits. Therefore, we proposed a hypothesis that UCP2may affect the Secretory function in the intestinal L cells. In this study, UCP2-/- mice were used to observe effect of UCP2 on GLP-1 and observe the effect of glucose on the expression of UCP2 as well as the change of GLP-1 secretion.AIM:To detect the distribution and expression of UCP2 in different intestinal tissues and assess the possible effect of UCP2 on GLP-1 secretion in the gastrointestinal tract. Methods:UCP2 mRNA and protein levels were detected in the gastrointestinal tract by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. Co-localization of UCP2 with GLP-1 was detected by immunohistochemistry staining. The level of serum GLP-1 was measured by a GLP-1 enzyme-linked immunoassay kit.Results:UCP2 was primarily expressed in mucosal epithelial cells and co-localized with GLP-1 in gastrointestinal mucosa. After glucose administration, expression of UCP2 was strongly induced in colon of C57BL/6J mice. UCP2-deficient mice showed an increased glucose-induced GLP-1 secretion compared to the littermates. Taken together, these results suggest an inhibitory role for UCP2 in glucose-induced GLP-1 secretion.Conclusion:The expression of UCP2 was strongly induced by glucose in mouse gastrointestinal tract.UCP2 serves as a negative regulator in glucose-induced GLP-1 secretion.