Protection of insulinlike growth factor 1 on experimental peripheral neuropathy in diabetic mice.
Mol Med Rep
; 18(5): 4577-4586, 2018 Nov.
Article
em En
| MEDLINE
| ID: mdl-30221656
ABSTRACT
The present study investigated whether insulinlike growth factor1 (IGF1) 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), IGF1treated db/db and IGF1picropodophyllin (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 IGF1 receptor (IGF1R), cJun Nterminal kinase (JNK), extracellular signalregulated kinase (ERK), p38 and effect of IGF1 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)IGF1. The sciatic NCV in the diabetes group was significantly lower compared with the control group. The sciatic NCV improved following rIGF1 intervention; however, was impaired following administration of the IGF1 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 rIGF1treated group was significantly improved compared with the diabetes group; whereas, they were significantly impaired following administration of the IGF1R inhibitor. In addition, the expression of IGF1R, phosphorylated (p)JNK and pERK of sciatic nerves in the db/db mice was significantly increased following treatment with IGF1. The expression levels of these proteins were significantly lower in the IGF1PPP group compared with the IGF1 group; however, no significant difference was observed in the expression levels of pp38 following treatment with IGF1. The results of the present study demonstrated that IGF1 may improve neuropathy in diabetic mice. This IGF1induced neurotrophic effect may be associated with the increased phosphorylation levels of JNK and ERK, not p38; however, it was attenuated by administration of an IGF1R antagonist.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes
/
Fator de Crescimento Insulin-Like I
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Diabetes Mellitus Experimental
/
Neuropatias Diabéticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article