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. Author manuscript; available in PMC: 2020 Mar 1.
Published in final edited form as: Pharmacol Ther. 2018 Oct 19;195:100–110. doi: 10.1016/j.pharmthera.2018.10.010

Figure 2. Role of 12-LOX and metabolites in beta cell demise.

Figure 2.

The figure depicts the pathways activated by 12-LOX in the pancreatic islet beta cell in response to elevated glucose levels, saturated free fatty acids, or PIC. 12-LOX activation leads to the production of pro-inflammatory lipid intermediates (12(S)-hydroperoxyeicosatetraenoic acid and 12(S)-HETE). These intermediates trigger subsequent inflammatory pathways mediated by c-Jun N-terminal kinase, p38-MAPK, and NOX. 12(S)-HETE prevents translocation of Nrf2 as well. Signaling through these pathways leads to increased ROS, oxidative stress, ER stress, which eventually cause beta cell dysfunction and death. Although not depicted in this diagram, other lipid mediators such as LPA and LPC contribute to MCP-1 mediated chemotaxy; ceramides contribute to beta-cell death, etc. FFAR, free fatty acid receptor; PLA, phospholipase A2; PGE2, prostaglandin E2; MCP1, monocyte chemoattractant protein 1.