LOX-1-mediated injury in sensory neurons in type 2 diabetes

• Published in: Dubai diabetes and endocrinology journal Vol. 20; no. 2; pp. 59 - 63
• Main Authors: Vincent, Andrea M., McLean, Lisa L., Pande, Manjusha, Su Oh, Sang, Feldman, Eva L.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.03.2019
• Subjects: SHORT REPORT; Sensory neurons; type 2 diabetes; Lipid metabolism genes; LOX-1
• ISSN: 2673-1797; 1606-7754; 2673-1738; 2073-5944
• DOI: 10.1159/000497727

Our laboratory recently identified several differentially expressed genes (DEG) through microarray analysis of the sciatic nerves of 24-week-old BKS db/db (diabetic) and db/+ (nondiabetic) mice. We noted prominent increases in lipid metabolism genes, consistent with another model, the high fat-fed C57BL6/J mouse, where we postulated that oxidized low-density lipoproteins (oxLDL) activate a receptor-mediated inflammatory pathway of neuronal injury. Our findings support clinical observations that plasma lipids associate with neuropathy, and suggest that glucose and lipids together will be responsible for the most aggressive development of diabetic neuropathy. A role for oxLDL-induced injury remains to be proved in vivo, and this is the goal of the present study. First, we performed biostatistical network analysis to identify molecular interactions of our LOX-1 gene of interest, Olr1. Next, nondiabetic BKSdb/+ and diabetic BKSdb/db littermates received intraperitoneal injections of LOX-1 neutralizing antibody or control non-immune IgG every 48 h from 6-12 wk of age. At 12 wk of age, blood and tissues were harvested for metabolic and neuropathy phenotyping. We confirmed our network analysis by demonstrating that NFkappaB, a gene closely linked to Olr1 in our network, was decreased in anti-LOX-1 treated mice. Most metabolic parameters (blood glucose, glycated hemoglobin, plasma triglycerides and cholesterol) and also the sciatic motor nerve conduction velocity deficit were unchanged in the presence of anti-LOX-1 treatment compared with control IgG. However, there was a striking preservation of the sural nerve conduction velocity in anti-LOX-1-treated mice, demonstrating that this receptor is involved in sural nerve injury in type 2 diabetes.