MiR-26a and miR-26b downregulate the expression of sucrase-isomaltase enzyme: A new chapter in diabetes treatment

Abstract

Type II diabetes is a metabolic disease that has affected 460 million people around the globe and become a heavy burden on health care system. Diabetic patients suffer from hyperglycemia and hyperinsulinemia which can damage vital organs in body like heart, kidneys, eyes and nervous system. Different strategies have been introduced to control or lessen these diabetic complications in which one of the most promising approaches is the inhibition of intestinal sucrase-isomaltase (SI). Inhibition of this enzyme will block the release of glucose into bloodstream and lead to reduced postprandial hyperglycemia. MicroRNAs are small regulatory molecules that play critical roles in different cellular pathways and molecular mechanisms. It is proved that microRNAs have significant effects on cellular mechanisms involved in diabetes and can be used as biomarkers for diagnosis of this metabolic disease. Based on bioinformatics analysis miR-26a and miR-26b can interact with a conserved 3′-UTR region of SI mRNA which lead to a hypothesis that these miRs may have negative regulatory effect on this enzyme. In this study, we investigated the impact of high glucose conditions on expression of sucrase-isomaltase, miR-26a and miR-26b in caco-2 cell line. It is proved that in a simulated diabetic condition there is a reverse correlation between the expression pattern of these miRs and SI. QRT-PCR method was used to evaluate the expression of our target molecules. Interestingly, transfection of miR-26a and miR-26b in caco-2 cell line reduced the transcription of SI mRNA and decreased the sucrase and maltase activity of its active sites. To sum up, our results demonstrate the first evidence of the significant effect of miR-26a and miR-26b on SI expression and activity. We proved that these microRNAs may directly inhibit this enzyme and can be used as a new scaffold in search of finding novel treatments for type II diabetes.