Table 2.

Summary of current evidence for 12-lipoxygenase (12-LOX) involvement in diabetes

Islet inflammation: Interleukin-1 beta regulates the expression of a leukocyte type of 12-LOX in rat islets and RIN m5F cells [43]. Defect in glucose-stimulated insulin secretion in both rodents and human islets: 12-LOX products reduce insulin secretion and β cell viability in human islets [30]. Insulin resistance on high-fat fed diet in rodents: 12/15-LOX is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice [36]. β cell apoptosis: Evidence that increased 12-LOX expression impairs pancreatic β cell function and viability [31, 45]. Activation of oxidative stress and/or mitochondrial dysfunction in islets: 12-HETE increases mitochondrial nitric oxide by increasing intramitochondrial calcium [46]. Activation of stress kinase pathways such as MAPK and JUNK in islets: The stress-activated c-Jun protein kinase (JNK) is stimulated by LOX pathway product 12-HETE in RIN m5F cells [44]. Autoimmune destruction of islets by activation of Th1 response in type 1 diabetes: Non-obese diabetic (NOD) mice congenic for a targeted deletion of 12/15-LOX are protected from autoimmune diabetes [38].