Melatonin reduces lung injury in type 1 diabetic mice by the modulation of autophagy.

In recent years, the role of autophagy has been highlighted in the pathogenesis of diabetes and inflammatory lung diseases. In this study, using a diabetic model of mice, we investigated the expression of autophagy-related genes in the lung tissues following melatonin administration. Data showed histopathological remodeling in lung tissues of the D group coincided with an elevated level of IL-6, Becline-1, LC3, and P62 compared to the control group (p < 0.05). After melatonin treatment, histopathological remodeling was improved D + Mel group. In addition, expression levels of IL-6, Becline-1, LC3, and P62 were decreased in D + Mel compared to D group (P < 0.05). Statistically significant differences were not obtained between Mel group and C group (p > 0.05). Our results showed that melatonin injection can be effective in the amelioration of lung injury in diabetic mice presumably by modulating autophagy-related genes.

Rezaie J ，Jahanghiri M ，Heris RM ，Hassannezhad S ，Abdyazdani N ，Rahbarghazi A ，Ahmadi M ... -  《BMC Molecular and Cell Biology》

Melatonin protects endothelial progenitor cells against AGE-induced apoptosis via autophagy flux stimulation and promotes wound healing in diabetic mice.

Jin H ，Zhang Z ，Wang C ，Tang Q ，Wang J ，Bai X ，Wang Q ，Nisar M ，Tian N ，Wang Q ，Mao C ，Zhang X ，Wang X ... -  《-》

Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ-induced diabetic mice.

Diabetes mellitus (DM) patients are at a higher risk of developing brain injury characterized by neuronal death. Melatonin, a hormone produced by the pineal gland, exerts neuroprotective effects against brain damage. However, the effect of melatonin on diabetes-induced brain injury has not been elucidated. This study was to evaluate the role of melatonin against neuronal death in DM and to elucidate the underlying mechanisms. Herein, we found that melatonin administration significantly alleviated the neuronal death in both streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-treated neuronal cells. Melatonin inhibited neuronal pyroptosis and excessive autophagy, as evidenced by decreased levels of NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, LC3, Beclin1, and ATG12 both in vivo and in vitro. MicroRNA-214-3p (miR-214-3p) was decreased in DM mice and HG-treated cells, and such a downregulation was corrected by melatonin, which was accompanied by repression of caspase-1 and ATG12. Furthermore, downregulation of miR-214-3p abrogated the anti-pyroptotic and anti-autophagic actions of melatonin in vitro. Our results indicate that melatonin exhibits a neuroprotective effect by inhibiting neuronal pyroptosis and excessive autophagy through modulating the miR-214-3p/caspase-1 and miR-214-3p/ATG12 axes, respectively, and it might be a potential agent for the treatment of brain damage in the setting of DM.

Che H ，Li H ，Li Y ，Wang YQ ，Yang ZY ，Wang RL ，Wang LH ... -  《-》

Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway.

Zhang S ，Tian W ，Duan X ，Zhang Q ，Cao L ，Liu C ，Li G ，Wang Z ，Zhang J ，Li J ，Yang L ，Gao Y ，Xu Y ，Liu J ，Yan J ，Cui J ，Feng L ，Liu C ，Shen Y ，Qi Z ... -  《Cardiovascular Diabetology》

Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function.

The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex. By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-β1, interleukin (IL)-1β, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.

Hajam YA ，Rai S ，Pandi-Perumal SR ，Brown GM ，Reiter RJ ，Cardinali DP ... -  《-》