| First Author | Wijesekara N | Year | 2012 |
| Journal | Diabetes | Volume | 61 |
| Issue | 3 | Pages | 653-8 |
| PubMed ID | 22315319 | Mgi Jnum | J:196746 |
| Mgi Id | MGI:5489842 | Doi | 10.2337/db11-0944 |
| Citation | Wijesekara N, et al. (2012) miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets. Diabetes 61(3):653-8 |
| abstractText | Changes in cellular cholesterol affect insulin secretion, and beta-cell-specific deletion or loss-of-function mutations in the cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) result in impaired glucose tolerance and beta-cell dysfunction. Upregulation of ABCA1 expression may therefore be beneficial for the maintenance of normal islet function in diabetes. Studies suggest that microRNA-33a (miR-33a) expression inversely correlates with ABCA1 expression in hepatocytes and macrophages. We examined whether miR-33a regulates ABCA1 expression in pancreatic islets, thereby affecting cholesterol accumulation and insulin secretion. Adenoviral miR-33a overexpression in human or mouse islets reduced ABCA1 expression, decreased glucose-stimulated insulin secretion, and increased cholesterol levels. The miR-33a-induced reduction in insulin secretion was rescued by cholesterol depletion by methyl-beta-cyclodextrin or mevastatin. Inhibition of miR-33a expression in apolipoprotein E knockout islets and ABCA1 overexpression in beta-cell-specific ABCA1 knockout islets rescued normal insulin secretion and reduced islet cholesterol. These findings confirm the critical role of beta-cell ABCA1 in islet cholesterol homeostasis and beta-cell function and highlight modulation of beta-cell miR-33a expression as a means to influence insulin secretion. |
