Impact of L-Arginine on diabetes-induced neuropathy and myopathy: Roles of PAI-1, Irisin, oxidative stress, NF-κβ, autophagy and microRNA-29a

Abstract

Background: T2DM is a chronic disorder with progressive neuromuscular alterations. L-arginine (ARG) is the most common semi-essential amino acid having several metabolic functions.

Aim: to investigate the impact of L-arginine in combating diabetic-induced neuromyopathy and its possible mechanisms.

Materials & methods: 24 rats were divided into CON, CON+ARG, DC, DC+ARG. Behavioral tests, Body weight (BW), fasting blood glucose (FBG), insulin, total antioxidant capacity (TAC), malondialdehyde (MDA), plasminogen activator inhibitor-1 (PAI-1), and irisin were done. Creatine kinase-MM (CK-MM), interleukin 4 (IL-4), interleukin 6 (IL-6), TAC, MDA, expression of microRNA-29a mRNA & light chain 3 protein were determined in muscle. Histological and NF-κβ immunohistochemical expression in muscle and nerve were assessed.

Results: ARG supplementation to diabetic rats improved altered behavior, significantly increased BW, insulin, TAC, irisin and Il-4, decreased levels of glucose, microRNA-29a, NF-κβ and LC3 expression, PAI-1, CK-MM and restored the normal histological appearance.

Conclusions: ARG supplementation potently alleviated diabetic-induced neuromuscular alterations.

Keywords: ARG; Irisin; LC3; MicroRNA-29a; NF-kβ; PAI-1; T2DM.