Lipid Mediators Are Critical in Resolving Inflammation: A Review of the Emerging Roles of Eicosanoids in Diabetes Mellitus

Figure 2

Eicosanoid compounds affect different organs in diabetes complications. Diabetic nephropathy, one of the most common complications in diabetes, shows low PGE₂ levels and altered glomerular hemodynamics. This dilates arteries and increases microvascular permeability. In normal conditions PGE₂ downregulates TNF-α production and upregulates IL-10 production through EP2 and EP4 receptor signaling. However, a proinflammatory environment leads to cell permeabilization, low concentrations of PGE₂, and mesangial cell proliferation. Diabetic retinopathy is another common complication in diabetes. In diabetes, the environment in the retina has a particular lipid profile, with higher COX-2 and abnormal production of PG. LTA₄ and LTB₄ are enhanced in addition to IL-8. Diabetic peripheral neuropathy is correlated with high COX-2 and PGE₂. In a diabetic’s cardiovascular system, PGE₂ has an important role in microvascular permeability, and 12-HETE and 20-HETE lower the activity of endothelial progenitor cell (EPC) function.