Effect of selective cyclooxygenase-2 (COX-2) inhibitor treatment on glucose-stimulated insulin secretion in C57BL/6 mice.
Previous studies have shown that Prostaglandin E(2) (PGE(2)) inhibits glucose-stimulated insulin secretion. However, the role of cyclooxygenase (COX)-1 vs. COX-2 derived PGE(2) production in glucose-stimulated insulin secretion remains poorly understood. Here we investigated the expression of COX-1 and COX-2 in pancreatic islets and the effect of selective inhibition of COX-1 and COX-2 on glucose-stimulated insulin secretion using C57BL/6 (B6) mice. Although immunofluorescence histochemistry showed the constitutive expression of both COX-1 and COX-2 in B6 mouse pancreatic islets, insulin secretion and hyperglycemia after glucose loading were ameliorated in B6 mice treated with selective COX-2 inhibitor (SC58236) for 18 weeks. Interestingly, incubation with selective COX-2 inhibitor for 24h led to a reduction in PGE(2) production in pancreatic islets isolated from B6 mice. In addition, selective COX-2 inhibition enhanced insulin secretion from the isolated islets. These results collectively suggest that selective inhibition of COX-2 enhances glucose-stimulated insulin secretion through a reduction in PGE(2) production in pancreatic islets.
Fujita
Hiroki
H
Division of Endocrinology, Metabolism and Geriatric Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. hirofuji@gipc.akita-u.ac.jp
Kakei
Masafumi
M
Fujishima
Hiromi
H
Morii
Tsukasa
T
Yamada
Yuichiro
Y
Qi
Zhonghua
Z
Breyer
Matthew D
MD
D000818:Animals; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL