Prostaglandin E2 mediates inhibition of insulin secretion by interleukin-1β

Phuong Oanh T. Tran, Catherine E. Gleason, Vincent Poitout, R. Paul Robertson

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Interleukin-1β (IL-1β) and prostaglandin E2 (PGE2), frequently co- participants in inflammatory states, are two well recognized inhibitors of glucose-induced insulin secretion. Previous reports have concluded that the inhibitory effects of these two autacoids on pancreatic β cell function are not related because indomethacin, a potent prostaglandin synthesis inhibitor, does not prevent IL-1β effects. However, indomethacin is not a specific cyclooxygenase inhibitor, and its other pharmacologic effects are likely to inhibit insulin secretion independently. Since we recently observed that IL- 1β induces cyclooxygenase-2 (COX-2) gene expression and PGE2 synthesis in islet β cells, we have reassessed the possibility that PGE2 synthesis in islet β cells, we have reassessed the possibility that PGE2 mediates IL-1β effects on β function. By using two cell lines (HIT-T15 and βHC13) as well as Wistar rat isolated pancreatic islets, we examined the ability of two COX- 2-specific antagonists, NS-398 and SC-236, to prevent IL-1β inhibition of insulin secretion. Both drugs prevented IL-1β from inducing PGE2 synthesis and inhibiting insulin secretion; adding back exogenous PGE2 re-established inhibition of insulin secretion in the presence of IL-1β. We also found that EP3, the PGE2 receptor subtype whose post-receptor effect is to decrease adenylyl cyclase activity and, thereby, insulin secretion, is the dominant mRNA subtype expressed. We conclude that endogenous PGE2 mediates the inhibitory effects of exogenous IL-1β on β cell function.

Original languageEnglish (US)
Pages (from-to)31245-31248
Number of pages4
JournalJournal of Biological Chemistry
Issue number44
StatePublished - Oct 29 1999

Fingerprint Dive into the research topics of 'Prostaglandin E<sub>2</sub> mediates inhibition of insulin secretion by interleukin-1β'. Together they form a unique fingerprint.

Cite this