Up-Regulated Pancreatic Tissue MicroRNA-375 Associates With Human Type 2 Diabetes Through β-Cell Deficit and Islet Amyloid Deposition

OBJECTIVES: The aim of this study was to examine correlations of the islet-specific microRNA-375 expression to islet amyloid formation and pancreatic islet damage in human type 2 diabetes. METHODS: Autopsy pancreas samples from 40 type 2 diabetic and 15 nondiabetic patients were used to detect microRNA-375 expression using real-time quantitative polymerase chain reaction. Serial paraffin sections of the corresponding type 2 diabetic and nondiabetic cases were stained by immunofluorescence to evaluate for amylin expression, amyloid formation, and proportions of alpha and beta cells. RESULTS: Pancreatic microRNA-375 expression was increased in type 2 diabetic patients comparing with the nondiabetic patients (median, 4.02 for the diabetic patients vs 0.92 for the nondiabetic patients; P = 0.0001). The median was 6.14 for the diabetic patients with islet amyloid and 3.51 for islet amyloid-free diabetic patients. The expression level of microRNA-375 correlated positively with the frequency and the severity of islet amyloid formation and negatively with proportions of islet beta-cells and amylin-positive area, and islet mitochondria density. CONCLUSIONS: Up-regulated microRNA-375 is associated with type 2 diabetes and pancreatic islet amyloid formation and beta-cell deficit. microRNA-375 may serve as a biomarker for known and novel pathways in the pathogenesis of type 2 diabetes related to islet amyloid deposition and beta-cell dysfunction.