Melatonin (MLT) is a biologically active indoleamine involved in regulating various biological rhythms, which is deficient in individuals with Type 2 diabetes. The present study examined the effects of MLT on diabetic neuropathy (DN). Diabetic rats received MLT treatment for 12 weeks, after which changes in kidney histology, oxidative damage, mitochondrial morphology and autophagy were measured. The glucose tolerance‑ and isoflurane tolerance‑area under the curve (AUC) values and the relative renal weight index (RI) in the diabetes mellitus (DM) group of rats were significantly higher compared with those in the control group. A significant increase in malondialdehyde (MDA) content, and decreases in the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‑Px) and GSH were demonstrated in the kidneys of DM rats compared with those in the control rats. Histological staining of DM rat kidney tissue with hematoxylin and eosin, Masson's trichome and Periodic acid‑Schiff demonstrated glomerular and tubule lesions, and an increase in collagen compared with control rats. Protein expression levels of LC3II, P62, collagen IV (COL‑IV) and α‑SMA were increased in DM rats and HG‑induced NRK‑52E cells compared with those in the control groups. Phosphorylation of AMPK was reduced, whereas phosphorylation of PI3K, Akt and mTOR were increased in vivo and in vitro. Notably, MLT treatment significantly reduced glucose tolerance‑AUC and RI, decreased MDA content, and increased SOD, CAT, GSH‑Px and GSH activity. Glomerular and tubule lesions improved, collagen was decreased and mitochondrial damage was alleviated by MLT treatment. MLT treatment also decreased the protein expression levels of LC3II, P62 and COL‑IV, whereas the phosphorylation of AMPK was significantly increased, which inhibited the phosphorylation of PI3K, AKT and mTOR in vivo and in vitro. These results demonstrated that MLT protects against DN and NRK‑52E cell injury through inhibiting oxidative damage and regulating autophagy via the PI3K/AKT/mTOR signaling pathway.
Keywords: autophagy; diabetes mellitus; kidney injury; melatonin.