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Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

Diabetes is a chronic disease that manifests when insulin production by the pancreas is insufficient or when the body cannot effectively utilize the secreted insulin. The onset of diabetes often goes undetected until the later stages where subsequent glucose accumulation in the system (hyperglycemia) is observed. Over time, it leads to serious multi-organ damage, especially to the nerves and blood vessels. The WHO reports that approximately 346 million people worldwide are diagnosed with diabetes. With no cure available, long-term medical care for diabetes has become a global economic challenge globally. Hence, there is a need to explore novel early biomarkers and therapeutics for diabetes. One such potential molecule is the miRNAs. miRNAs are endogenous, noncoding RNAs that predominantly inhibit gene expression. Compelling evidence showed that altered miRNA expressions are linked to pathological conditions, including diabetes manifestation. This review focuses on the implications of miRNAs in diabetes and their related complications. INSET: Key issues. [ABSTRACT FROM AUTHOR]