Prostaglandin E2 stimulates GLP-1 and GLP-2 secretion and reduces glucose absorption in the perfused rat small intestine.

Prostaglandins (PGs) are paracrine mediators derived from arachidonic acid. In the gut, they regulate mucosal integrity, epithelial function, and inflammation. Glucose and possibly also prostaglandin E2 (PGE2) stimulate the release of glucagon-like peptide 1 (GLP-1). As PGE2 has been reported to modulate intestinal glucose absorption, the aim of this study was to investigate the acute effect of PGE2 on GLP-1 and GLP-2 secretion as well as intestinal glucose absorption using a physiologically relevant experimental setup-the isolated perfused rat small intestine. Two protocols were employed: A, luminal glucose instillation before and during an intra-arterial infusion of PGE2 (10 µmol/L); and B, same as protocol A, but with the COX inhibitor indomethacin (10 µmol/L) included in the perfusion buffer to block endogenous PG production. Administration of PGE2 stimulated the release of GLP-1 (2.1-fold; P = .002) and GLP-2 (2.5-fold; P = .002) from the perfused intestine vs vehicle. Inclusion of indomethacin in the perfusion buffer neither affected GLP-1 and GLP-2 secretion nor responses to PGE2, consistent with minimal production of PGs in the noninflamed in situ-perfused intestine. We observed a decrease in glucose absorption during administration of PGE2 vs vehicle (P = .043). PGE2 stimulates the secretion of GLP-1 and GLP-2, adding to its established roles in intestinal physiology. Acute administration of PGE2 significantly attenuated small intestinal glucose absorption. Our data confirm that PGE2 stimulates gut hormone release, which could be responsible for some of the effects ascribed to PGE2 and might explain the adverse effects associated with the inhibition of PG synthesis with nonsteroidal anti-inflammatory drugs.