Protection of insulin‑like growth factor 1 on experimental peripheral neuropathy in diabetic mice.

The present study investigated whether insulin‑like growth factor‑1 (IGF‑1) exerts a protective effect against neuropathy in diabetic mice and its potential underlying mechanisms. Mice were divided into four groups: Db/m (control), db/db (diabetes), IGF‑1‑treated db/db and IGF‑1‑picropodophyllin (PPP)‑treated db/db. Behavioral studies were conducted using the hot plate and von Frey methods at 6 weeks of age prior to treatment. The motor nerve conduction velocity (NCV) of the sciatic nerve was measured using a neurophysiological method at 8 weeks of age. The alterations in the expression levels of IGF‑1 receptor (IGF‑1R), c‑Jun N‑terminal kinase (JNK), extracellular signal‑regulated kinase (ERK), p38 and effect of IGF‑1 on the sciatic nerve morphology were observed by western blotting and electron microscopy. Compared with the control group, the diabetes group developed hypoalgesia after 12 weeks, and neurological lesions improved following an intraperitoneal injection of recombinant (r)IGF‑1. The sciatic NCV in the diabetes group was significantly lower compared with the control group. The sciatic NCV improved following rIGF‑1 intervention; however, was impaired following administration of the IGF‑1 receptor antagonist, PPP. The myelin sheath in the sciatic nerve of the diabetes group was significantly more impaired compared with the control group. The myelin sheath in the sciatic nerves of the rIGF‑1‑treated group was significantly improved compared with the diabetes group; whereas, they were significantly impaired following administration of the IGF‑1R inhibitor. In addition, the expression of IGF‑1R, phosphorylated (p)‑JNK and p‑ERK of sciatic nerves in the db/db mice was significantly increased following treatment with IGF‑1. The expression levels of these proteins were significantly lower in the IGF‑1‑PPP group compared with the IGF‑1 group; however, no significant difference was observed in the expression levels of p‑p38 following treatment with IGF‑1. The results of the present study demonstrated that IGF‑1 may improve neuropathy in diabetic mice. This IGF‑1‑induced neurotrophic effect may be associated with the increased phosphorylation levels of JNK and ERK, not p38; however, it was attenuated by administration of an IGF‑1R antagonist.