Liraglutide Enhances Autophagy and Promotes Pancreatic β Cell Proliferation to Ameliorate Type 2 Diabetes in High-Fat-Fed and Streptozotocin-Treated Mice
Menglin Fan, Hongwei Jiang, Yingyu Zhang, Yujin Ma, Liping Li, Jiannan Wu
(Department of Endocrinology, First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China (mainland))
Med Sci Monit 2018; 24:2310-2316
Clinical and experimental studies have revealed that liraglutide has multiple anti-diabetes biological effects. However, little is known about its role in autophagy and pancreatic β cell proliferation. This study aimed to assessed the effects of liraglutide on pancreatic b cell proliferation and autophagy in a mouse model of type 2 diabetes.
MATERIAL AND METHODS: The effect of liraglutide on autophagy and proliferation in pancreatic β cells was investigated using a high-fat-fed and streptozotocin-induced mouse model of type 2 diabetes.
RESULTS: Liraglutide significantly improved the symptoms of high-fat-fed (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice, as indicated by body weight gain, reduction of blood glucose and plasma insulin, and enhanced sensitivity to insulin. The results of quantitative real-time polymerase chain reaction and Western blot analysis showed that liraglutide upregulated AGT5 expression and promoted the conversion of LC3-I to LC3-II, thus improving the defective autophagy. In addition, we observed that both mRNA and protein expressions of PCNA and Ki-67 were upregulated by liraglutide treatment. Immunocytochemical staining results showed that the number of PCNA- or Ki-67-positive cells in pancreatic islet tissues in the HFD + STZ + liraglutide group were increased compared with the HFD + STZ group.
CONCLUSIONS: These results strongly suggest that liraglutide is able to enhance autophagy and promote pancreatic β cell proliferation. This study improves our insights into the mechanism by which liraglutide treatment relieves diabetes, and provides experimental evidence for clinical utilization of liraglutide in type 2 diabetes treatment.
Keywords: Autophagy, Cell Proliferation, Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, Insulin-Secreting Cells, Cell Proliferation