miRNAs as biomarkers of IAPP-induced inflammation in type 2 diabetes
Janice Pang
Pinetree Secondary
Floor Location : S 233 H

Type 2 diabetes (T2D) is a chronic disease brought about by metabolic events such as insulin resistance and the progressive dysfunction of insulin-secreting ?-cells. Recently, both inflammation and islet amyloid polypeptide (IAPP) - a peptide that aggregates to form amyloid plaques - have been suggested to impair ?-cell function. Aggregation of human IAPP (hIAPP) has also been found to drive resident islet macrophages toward a proinflammatory phenotype. In addition, microRNAs (miRNA), which are small, noncoding RNAs, can regulate gene expression and lead to defective insulin secretion and ?-cell apoptosis upon exposure to proinflammatory cytokines. For this reason, miRNAs may be upregulated in response to IAPP-induced inflammation in pancreatic islets. More importantly, miRNAs may be potential novel biomarkers of IAPP-induced inflammation in T2D. Thus, in this study, wild-type and hIAPP transgenic islets were cultured for six days in high glucose (16.7 mM) to determine whether IAPP promotes upregulation of miR-375, miR-21, and miR-146a through an inflammatory pathway. Quantification of miRNA expression by qRT-PCR revealed that the expression of miR-21 and miR-146a, but not miR-375, was significantly increased in hIAPP transgenic islets compared to wild-type islets. In fact, results from the quantification of immunostaining indicate that miR-21, and miR-146a may be linked to IAPP aggregation in T2D. Collectively, these findings highlight a novel involvement of miR-21 and miR-146a in IAPP-induced inflammation, and identifies miR-21 and miR-146a as attractive biomarkers of T2D.