The Role of 12-lipoxygenase in Pancreatic -Cells (Review)

Int J Mol Med. 1998 Jan;1(1):265-72.

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.

Publication types

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

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / physiology*
  • Cytokines / toxicity
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Rats

Substances

  • Cytokines
  • Insulin
  • Arachidonate 12-Lipoxygenase
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat