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Dipeptidyl peptidase IV inhibitor potentiates duodenal bicarbonate secretion and prevents intestinal mucosal injury in rats
Author(s) -
Inoue Takuya,
Kaunitz Jonathan D,
Akiba Yasutada
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1068.1
Subject(s) - dipeptidyl peptidase 4 , dipeptidyl peptidase , glucagon like peptide 1 , chemistry , enteroendocrine cell , endocrinology , medicine , pharmacology , biology , biochemistry , enzyme , hormone , endocrine system , diabetes mellitus , type 2 diabetes
Luminal nutrients stimulate enteroendocrine cells, which release gut hormones, including glucagon‐like peptide‐2 (GLP‐2). Luminal co‐perfusion of L‐glutamate (L‐Glu) and 5′‐inosine monophosphate (IMP) synergistically increases duodenal bicarbonate secretion (DBS) via GLP‐2 release, rapidly degraded by dipeptidyl peptidase (DPP) IV. We thus hypothesized that DPPIV inhibition enhances luminal nutrient‐induced DBS and prevents intestinal injury. We measured DBS in a perfused rat duodenal loop. L‐Glu and IMP were co‐perfused +/− perfusion or iv injection of a selective DPPIV inhibitor NVP‐728. The effect of a long‐acting DPPIV inhibitor K579 (ig or ip) was also examined on indomethacin (IND)‐induced intestinal injury. DPPIV activity was highly present on the brush border and submucosal layer. L‐Glu/IMP perfusion increased DBS, inhibited by the GLP‐2 receptor antagonist. NVP‐728 iv enhanced the L‐Glu/IMP‐induced DBS, whereas perfused NVP‐728 had no effect, suggesting that submucosal DPPIV degrades GLP‐2. Pretreatment of K579 dose‐dependently reduced the index of IND‐induced intestinal ulcers. DPPIV inhibition potentiated L‐Glu/IMP‐induced DBS via GLP‐2 pathway and prevented intestinal injury, suggesting that the modulation of endogenous GLP‐2 by luminal nutrients and DPPIV inhibition may be therapeutic for intestinal mucosal injury and healing. Ajinomoto Inc, R01 DK54221