Cellular distribution and contribution of cyclooxygenase COX-2 to diabetogenesis in NOD mouse

Cell Tissue Res. 2002 Nov;310(2):169-75. doi: 10.1007/s00441-002-0628-6. Epub 2002 Aug 27.


Unlike most other mammalian cells, beta-cells of Langerhans constitutively express cyclooxygenase (COX)-2 rather than COX-1. COX-2 is also constitutively expressed in type 1 diabetes (T1D) patients' periphery blood monocytes and macrophage. To understand the role of COX-2 in the beta-cell, we investigated COX-2 expression in beta-cells and islet infiltrates of NOD and BALB/c mice using fluorescence immunohistochemistry and cytochemical confocal microscopy and Western blotting. Immunostaining showed that COX-2 is expressed in islet-infiltrating macrophages, and that the expression of insulin and COX-2 disappeared concomitantly from the beta-cells when NOD mice progressed toward overt diabetes. Also cultured INS-1E cells coexpressed insulin and COX-2 but clearly in different subcellular compartments. Treatment with celecoxib increased insulin release from these cells in a dose-dependent manner in glucose concentrations ranging from 5 to 17 mM. Excessive COX-2 expression by the islet-infiltrating macrophages may contribute to the beta-cell death during insulitis. The effects of celecoxib on INS-1E cells suggest that PGE(2) and other downstream products of COX-2 may contribute to the regulation of insulin release from the beta-cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Celecoxib
  • Cell Compartmentation
  • Cell Line
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Diabetes Mellitus, Type 1 / enzymology*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression
  • Immunohistochemistry
  • Insulin / genetics
  • Insulin / metabolism
  • Islets of Langerhans / cytology
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Pancreas / cytology
  • Pancreas / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Pyrazoles
  • Sulfonamides / pharmacology


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Insulin
  • Isoenzymes
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib