Circulating microRNA-375 as biomarker of pancreatic beta cell death and protection of beta cell mass by cytoprotective compounds

• Published in: PloS one 2017-10, Vol.12 (10), p.e0186480-e0186480
• Main Authors: Song, Imane, Roels, Sarah, Martens, Geert A, Bouwens, Luc
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Beta cells; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Blood; Blood circulation; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood plasma; Care and treatment; Cell death; Cell Line; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; DNA methylation; Drugs; Gene expression; Genetic aspects; Glucose; Glucosides - pharmacology; Hypoglycemic Agents - pharmacology; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Male; Medical imaging; Medicine and Health Sciences; Methods; Mice; Mice, Inbred BALB C; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; miRNA; Mortality; Pancreas; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Pancreatic beta cells; Peptides - pharmacology; Phenylpropionates - pharmacology; Physiological aspects; Protective Agents - pharmacology; Ribonucleic acid; RNA; Streptozocin; Studies; Type 2 diabetes; Venoms - pharmacology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186480

Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug. PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death. Beta cell mass and apoptotic death were measured in pancreatic tissue sections. Circulating miR-375 was measured in blood plasma by RT-qPCR. The release of miR-375 was also measured in vitro by MIN-6 beta cells. Administration of STZ resulted in measurable circulating levels of miR-375, a decrease in beta cell mass and increase in frequency of apoptotic beta cells. In vitro, there was a good correlation between miR-375 release and the extent of beta cell death. Treatment of mice with PPAG or exendin-4 significantly attenuated STZ-induced loss of beta cell mass and beta cell apoptosis, and normalized the blood level of miR-375. These findings show the potential use of serological miR-375 measurements to evaluate the beta cytoprotective effect of (potential) antidiabetic drugs in vivo.