miR378a-3p in serum extracellular vesicles is associated with pancreatic beta-cell mass in diabetic states.

The condition in which the insulin secretory ability of pancreatic β-cells decreases in diabetes is extremely important, but there are currently no biomarkers that reflect pancreatic β-cell failure. Therefore, we conducted a search for biomarkers, using pancreatic β-cell-specific 3-Phosphoinositide-dependent protein kinase 1 (PDK1) knockout mice, which develop severe hyperglycemia due to a decrease in pancreatic β-cell mass without insulin resistance. The analysis was performed in young mice when metabolic abnormalities were not yet apparent. Comprehensive analysis of microRNAs contained in extracellular vesicles in the blood of these mice revealed that miR378a-3p levels were significantly lower in PDK1 knockout mice than in control mice. Furthermore, in other mouse models of diabetes, namely, db/db mice and streptozotocin-induced diabetic mice, there was an increase and decrease in miR378a-3p expression, respectively, in line with the number of β-cells. These results suggest that miR378a-3p contained in serum extracellular vesicles is a biomarker that reflects pancreatic β-cell mass before the onset of diabetes. It is hoped that miR378a-3p can be utilized to realize earlier diagnosis and treatment of diabetes.