Crocin ameliorates MicroRNAs-associated ER stress in type 2 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 (600 mg/kg/day, PO). On the fourteenth day, after proving hyperglycemia, crocin (15, 30, and 60 mg/kg) and metformin (MT) (150 mg/kg) were used for detoxification of MG until the end of the experiment. The animals were divided into 6 groups: 1) control, 2) diabetic by MG, 3) MG + crocin 15 mg/kg, 4) MG + crocin 30 mg/kg, 5) MG + crocin 60 mg/kg, and 6) MG + MT. The data were analyzed by one-way analysis of variance and significant differences were compared by Tukey and Bonferroni tests (P 0.05). Biochemical assays, antioxidant evaluation, and microRNAs expression associated with ER stress were assessed.Results: MG induced hyperglycemia, insulin resistance, and dyslipidemia (P 0.001). Crocin and MT significantly ameliorated β-cell function through reduction of fasting blood glucose, malondialdehyde levels (P 0.001), and  significant elevation of anti-oxidant enzyme activity accompanied by regulation of glutathione and glyoxalase1-Nrf2 in MG induced diabetic mice. Crocin and MT significantly down-regulated microRNAs 204, 216b, 192, and 29a expression (P 0.001). Crocin (60 mg/kg) (P 0.01) and MT (P 0.001) could improve diameter of pancreatic islets in MG treated mice. Conclusion: Crocin prevents the progression of diabetes through modulating ER stress-associated microRNAs and GLO1 activity with the helpful effects of glutathione and Nrf2.