| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 16, 2001
Accepted on May 22, 2002
1 Leslie and Susan Gonda (Goldschmied) Diabetes and Genetics Research Center Department of Diabetes, Endocrinology, & Metabolism City of Hope National Medical Center Duarte, CA 91010
* To whom correspondence should be addressed. E-mail: dbleich{at}coh.org.
Cyclooxygenase-2 (COX-2) gene and 12-lipoxygenase (12-LO) gene are preferentially expressed over other types of cyclooxygenase and lipoxygenase in pancreatic ß-cells. Inhibition of either COX-2 or 12-LO can prevent cytokine-induced pancreatic ß-cell dysfunction as defined by inhibition of glucose-stimulated insulin secretion. Since cellular stress induces both genes and their respective end products in pancreatic ß-cells, we evaluated the role of 12-hydroxyeicosatetraenoic acid (12-HETE) on COX-2 gene expression, protein expression, and prostaglandin E2 (PGE2) production.
We demonstrate that 12-HETE significantly increases COX-2 gene expression and consequent product formation, while a closely related lipid 15-hydroxyeicosatetraenoic acid (15-HETE), does not. In addition, interleukin-1ß stimulated prostaglandin E2 production is completely inhibited by a preferential lipoxygenase inhibitor cinnaminyl-3,4-dihydroxy-
-cyanocinnamate (CDC).
We then evaluated IL-1ß induced PGE2 production in islets purified from control C57BL/6 mice and 12-LO knockout mice lacking cytokine-inducible 12-HETE. IL-1ß stimulated an 8-fold increase in PGE2 production in C57BL/6 islets, but failed to stimulate PGE2 in 12-LO knockout islets. Addition of 12-HETE to 12-LO knockout islet cells produced a statistically significant rise in PGE2 production. Furthermore, 12-HETE, but not 15-HETE, stimulated COX-2 promoter and AP-1 binding activity. These data demonstrate that 12-HETE mediates cytokine-induced COX-2 gene transcription and resultant PGE2 production in pancreatic ß-cells.
This article has been cited by other articles:
 |
|
 |
|
  R. S. Deeb, R. K. Upmacis, B. D. Lamon, S. S. Gross, and D. P. Hajjar Maintaining Equilibrium by Selective Targeting of Cyclooxygenase Pathways: Promising Offensives Against Vascular Injury Hypertension, January 1, 2008; 51(1): 1 - 7. [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Persaud, D. Muller, V. D. Belin, I. Kitsou-Mylona, H. Asare-Anane, A. Papadimitriou, C. J. Burns, G. C. Huang, S. A. Amiel, and P. M. Jones The Role of Arachidonic Acid and Its Metabolites in Insulin Secretion From Human Islets of Langerhans Diabetes, January 1, 2007; 56(1): 197 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Owens, K. R. Shroyer, and T. T. Kingdom Expression of cyclooxygenase and lipoxygenase enzymes in nasal polyps of aspirin-sensitive and aspirin-tolerant patients. Arch Otolaryngol Head Neck Surg, June 1, 2006; 132(6): 579 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Natarajan and J. L. Nadler Lipid Inflammatory Mediators in Diabetic Vascular Disease Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1542 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Yang and D. Bleich Transcriptional Regulation of Cyclooxygenase-2 Gene in Pancreatic {beta}-Cells J. Biol. Chem., August 20, 2004; 279(34): 35403 - 35411. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
