FIG 8.

Proposed model of 12-LO action in the islet β cell. The figure depicts evidence from both published literature and the present study. High-fat diets (via cytokines, free fatty acids, and elevated blood glucose) activate 12-LO activity in β cells, which then leads to increased 12-HETE production. In the present study, we propose that 12-HETE and other lipid peroxide products of 12-LO suppresses the otherwise adaptive increase Nrf2 transcription and protein levels. As a result, antioxidant genes and their encoded proteins are suppressed, leading to failure of β cell adaptation and to glucose intolerance.