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17 April 2018 : Animal Research  

Liraglutide Enhances Autophagy and Promotes Pancreatic β Cell Proliferation to Ameliorate Type 2 Diabetes in High-Fat-Fed and Streptozotocin-Treated Mice

Menglin Fan1BCEF, Hongwei Jiang1ADG*, Yingyu Zhang1BCF, Yujin Ma1BF, Liping Li1F, Jiannan Wu2B

DOI: 10.12659/MSM.906286

Med Sci Monit 2018; 24: ANS2310-2316

Abstract

BACKGROUND: 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: Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, Insulin-Secreting Cells

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750