, Volume 310, Issue 2, pp 169-175

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

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Unlike most other mammalian cells, β-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 β-cell, we investigated COX-2 expression in β-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 β-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 β-cell death during insulitis. The effects of celecoxib on INS-1E cells suggest that PGE2 and other downstream products of COX-2 may contribute to the regulation of insulin release from the β-cells.