Embryonic stem cell-derived pancreatic endoderm transplant with MCT1-suppressing miR-495 attenuates type II diabetes in mice

Abstract

Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder resulting from defects in both insulin secretion and insulin activity. The deficit and dysfunction of insulin secreting β-cells are signature symptoms of T2D. Additionally, in pancreatic β-cells, a small group of genes that are abundantly expressed in most other tissues is highly selectively repressed. Monocarboxylate transporter 1 (MCT1) is one of these genes. In this study, we identified an MCT1-suppressing microRNA (hsa-miR-495) and used this microRNA together with human embryonic stem cell (hESC) derived pancreatic endoderm (PE) cells transplanted into a high-fat diet induced T2D mouse model. Glucose metabolism significantly improved and other symptoms of T2D were attenuated after the procedure. Our findings support the potential for T2D treatment using the combination of microRNA and hESC differentiated PE cells.