The role of 12-lipoxygenase in pancreatic -cells (Review).

  • Authors:
    • D Bleich
    • S Chen
    • J L Gu
    • J L Nadler
  • View Affiliations

  • Published online on: January 1, 1998     https://doi.org/10.3892/ijmm.1.1.265
  • Pages: 265-337
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Abstract

Leukocyte type 12-lipoxygenase (12-LO) catalyzes the conversion of arachidonic acid (AA; C20:4) to 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and linoleic acid (LA; C18:2) to 13-hydroperoxyoctadecadienoic acid (13-HPODE). Previous studies have demonstrated that 12-LO, but not 5- or 15-lipoxygenase (5-LO, 15-LO respectively), is specifically expressed in pancreatic -cells and is involved in regulating glucose-stimulated insulin secretion. Lipoxygenase products also have been linked with inflammatory pathways in endothelial cells, kidney mesangial cells, inflammatory bowel disease, and corneal epithelial cells. Therefore, 12-LO may play a role in cytokine mediated inflammation in pancreatic beta-cells (i.e. beta -cell dysfunction and cytotoxicity). Cytokines such as IL-1 stimulate both de novo 12-LO protein synthesis and enzyme activity in pancreatic beta-cells. The products generated by 12-LO may ultimately be involved in cellular events that lead to lipid peroxidation. Hydroperoxide and free radical production in beta-cells can activate intracellular signaling pathways that lead to cell death or may directly damage mitochondrial and plasma membranes. Increased 12-LO expression has also been found in islets from prediabetic Zucker fatty rats, a model that demonstrates insulin secretory defects similar to human type 2 diabetes. In this review, we present an overview of the 12-LO pathway in regulating glucose-stimulated insulin secretion in beta-cells as well as more recent data which supports the hypothesis that the 12-LO pathway participates in cytokine mediated beta-cell dysfunction and cytotoxicity.

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Jan 1998
Volume 1 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bleich D, Chen S, Gu J and Nadler J: The role of 12-lipoxygenase in pancreatic -cells (Review).. Int J Mol Med 1: 265-337, 1998.
APA
Bleich, D., Chen, S., Gu, J., & Nadler, J. (1998). The role of 12-lipoxygenase in pancreatic -cells (Review).. International Journal of Molecular Medicine, 1, 265-337. https://doi.org/10.3892/ijmm.1.1.265
MLA
Bleich, D., Chen, S., Gu, J., Nadler, J."The role of 12-lipoxygenase in pancreatic -cells (Review).". International Journal of Molecular Medicine 1.1 (1998): 265-337.
Chicago
Bleich, D., Chen, S., Gu, J., Nadler, J."The role of 12-lipoxygenase in pancreatic -cells (Review).". International Journal of Molecular Medicine 1, no. 1 (1998): 265-337. https://doi.org/10.3892/ijmm.1.1.265