TY - JOUR
T1 - Prostaglandin E2 mediates inhibition of insulin secretion by interleukin-1β
AU - Tran, Phuong Oanh T.
AU - Gleason, Catherine E.
AU - Poitout, Vincent
AU - Robertson, R. Paul
PY - 1999/10/29
Y1 - 1999/10/29
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.274.44.31245
DO - 10.1074/jbc.274.44.31245
M3 - Article
C2 - 10531320
AN - SCOPUS:0033615530
SN - 0021-9258
VL - 274
SP - 31245
EP - 31248
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -