Crocin ameliorates MicroRNAs-associated ER stress in type ۲ diabetes induced by methylglyoxal

Objective(s): Methylglyoxal (MG) provokes endoplasmic reticulum (ER) stress in β-cells and triggers pancreatic β-cell dysfunction. Crocin has anti-diabetic properties. The present study investigated whether crocin prevented pancreas damages induced by MG.Materials and Methods: Diabetes was induced by MG administration (۶۰۰ mg/kg/day, PO). On the fourteenth day, after proving hyperglycemia, crocin (۱۵, ۳۰, and ۶۰ mg/kg) and metformin (MT) (۱۵۰ mg/kg) were used for detoxification of MG until the end of the experiment. The animals were divided into ۶ groups: ۱) control, ۲) diabetic by MG, ۳) MG + crocin ۱۵ mg/kg, ۴) MG + crocin ۳۰ mg/kg, ۵) MG + crocin ۶۰ mg/kg, and ۶) MG + MT. The data were analyzed by one-way analysis of variance and significant differences were compared by Tukey and Bonferroni tests (P<۰.۰۵). Biochemical assays, antioxidant evaluation, and microRNAs expression associated with ER stress were assessed.Results: MG induced hyperglycemia, insulin resistance, and dyslipidemia (P<۰.۰۰۱). Crocin and MT significantly ameliorated β-cell function through reduction of fasting blood glucose, malondialdehyde levels (P<۰.۰۰۱), and  significant elevation of anti-oxidant enzyme activity accompanied by regulation of glutathione and glyoxalase۱-Nrf۲ in MG induced diabetic mice. Crocin and MT significantly down-regulated microRNAs ۲۰۴, ۲۱۶b, ۱۹۲, and ۲۹a expression (P<۰.۰۰۱). Crocin (۶۰ mg/kg) (P<۰.۰۱) and MT (P<۰.۰۰۱) could improve diameter of pancreatic islets in MG treated mice. Conclusion: Crocin prevents the progression of diabetes through modulating ER stress-associated microRNAs and GLO۱ activity with the helpful effects of glutathione and Nrf۲.

Keywords:

Crocin , Diabetes , ER stress , Glyoxalase ۱ , Methylglyoxal , miR-۲۰۴