Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration.

The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers

Preventive effect of ecabet sodium on low-dose aspirin-induced small intestinal mucosal injury: a randomized, double-blind, pilot study

Abstract Background We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers. Methods Healthy volunteers were enrolled randomly into one of two groups with the following drug regimens for 2 weeks: group A, low-dose aspirin once per day and group B, low-dose aspirin and 4.0 g of ecabet sodium. Small bowel capsule endoscopy was performed before and 2 weeks after low-dose aspirin administration. Results A significant difference was found in the median number [range] of small intestinal lesions between baseline and two weeks after low-dose aspirin administration in group A (baseline: 1 [0–5], after: 5 [1–11]; p = 0.0059) but not in group B (baseline: 0.5 [0–9], after: 3 [0–23]; p = 0.0586). In group B, although the median number [range] of lesions in the first tertile of the small intestine did not increase two weeks after low-dose aspirin administration (baseline: 0 [0–4], after: 1.5 [0–8]; p = 0.2969), the number of lesions in the second and third tertiles of the small intestine increased significantly (baseline: 0 [0–5], after: 2 [0–15]; p = 0.0469). Conclusions Ecabet sodium had a preventive effect on low-dose aspirin-induced small intestinal mucosal injury in the upper part of the small intestine. Trial registration ISRCTN 99322160, 01/10/2018

Progression of pancreatic branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) after surgery for extrapancreatic malignancies

Abstract Background/aims The natural history of pancreatic branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is still unknown. This retrospective study aims to determine the morphological changes of BD-IPMNs with attention to the history of surgical resection for extrapancreatic malignancies. Methods and materials This study included 427 subjects with BD-IPMN at the Osaka Medical College from January 2001 to December 2019; 134 patients were included. The predictive factors for the progression of BD-IPMN based on morphological changes were evaluated by univariate as well as multivariate analyses. Furthermore, the clinical features of BD-IPMNs with progressive lesions during follow-up were investigated. Results The average interval of follow-up was 35.8 months (with a range between 12.1 and 157 months). Disease progression occurred in 6 subjects (4.5%). In two of them (1.5%), IPMN-related invasive carcinoma was found. Multivariate analysis demonstrated that surgical resection for extrapancreatic malignancies was a significant predictor of BD-IPMN progression. Conclusion The history of resection of extrapancreatic malignancies should be considered during the follow-up of BD-IPMN