A1 Journal article – refereed
Cellular distribution and contribution of cyclooxygenase (COX)-2 to diabetogenesis in NOD mouse




List of Authors: Luo C, Kallajoki M, Gross R, Mulari M, Teros T, Ylinen L, Makinen M, Laine J, Simell O
Publisher: SPRINGER-VERLAG
Publication year: 2002
Journal: Cell and Tissue Research
Journal name in source: CELL AND TISSUE RESEARCH
Journal acronym: CELL TISSUE RES
Volume number: 310
Issue number: 2
ISSN: 0302-766X

Abstract
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 cells.

Last updated on 2019-21-08 at 21:40