Increased sciatic NF-kB and decreased VEGF-A levels contributes to neuropathy in diabetes associated with decreased angiogenesis: Rescue effect of IGF-1

Background and Objective: Nowadays, diabetic neuropathy remains the most severe form of complications that affects 40–50 % of people in the world. Insulin-like growth factor-1 (IGF-1) is a peptide hormone structurally related to insulin that exerts potent proliferative, angiogenic and antiapoptotic effects in target tissues. Also, IGF-1 deficiency is common in type 1 diabetes and due to this decrease; sensitivity of the cells to insulin also decreases. This study was aimed to characterize the angiogenesis alterations and the molecular mediators which are related to angiogenesis in the sciatic nerve under diabetes condition and IGF-1 therapy. Materials and Methods: 21 male Wistar rats were assigned into 3 groups, namely control, diabetes and diabetes +IGF-I. Type 1 diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. After 30 days of treatment with IGF-I, diabetic neuropathy was evaluated by hot plate, HbA1c was measured, angiogenesis was determined by immunostaining for PECAM-1/CD31 and expressions of VEGF-A and NF-kB levels were also determined by the ELISA method. Findings: After four weeks, diabetes group showed a significant (P<0.001) decrease in capillary density, VEGF-A levels and significant (p < 0. 001) increase in HbA1c , NF- kB levels in sciatic nerve and a significant (p < 0. 001) decrease in reaction time compared to the control group, whereas these effects were reversed by IGF-I. Conclusion: These findings indicate that diabetes-induced neuropathy may in part be associated with decreased angiogenesis mediated by overproduction of NF- kB and downproduction of VEGF-A proteins. It also shows that IGF-1 can reduce neuropathy followed by increased angiogenesis by change of NF- kB and VEGF-A production levels.

Keywords:

Diabetes , Neuropathy , IGF-1.