J Biol Regul Homeost Agents. 2019 Jan-Feb;33(1):133-138.
Effect of glucagon-like peptide-1 on autophagy of islet β cells in type 2 diabetic mice with high fat diet.
- 1 Department of Endocrinology, Zhuji People’s Hospital, Zhuji City, China.
The aim of this study was to investigate the effect of glucagon-like peptide-1 (GLP-1) on islet β-cell autophagy in mice with type 2 diabetes induced by high-fat diet and low-dose streptozotocin (STZ). Twenty-four 6-week-old male C57BL/6J mice were divided into four groups: group A (control group; 8-week low-fat diet and 8-week normal saline treatment), group B (8-week high fat diet and streptozotocin intervention as well as 8-week normal saline treatment), group C (8-week high fat diet and streptozotocin intervention as well as 2-week GLP-1 intervention), and D (8-week high fat diet and streptozotocin intervention as well as 8-week GLP-1 intervention), with six mice in each group. At the end of 16-weeks, the mice were sacrificed, and blood and tissues were collected. The pathophysiological and morphological changes were evaluated by H and E staining. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) was performed. Autophagy in islet cells was accessed by immunofluorescence staining of LC3 and P62. Glucose tolerance test (GTT) showed that blood glucose was lower in group C than in group B at 60 min after fasting and glucose load (P less than 0.05). Insulin tolerance test (ITT) showed that blood glucose in group C was lower than that in group B at 30 min, 60 min, and 120 min, respectively (P less than 0.05). H and E staining showed that the hepatic steatosis, necrosis and inflammatory cell infiltration were significantly reduced in group D compared with group A, B and C (P less than 0.05); mice in group B had the highest degree of islet morphological changes, cell necrosis, and inflammatory cell infiltration among the four groups (P less than 0.05). The level of LC3 was higher in group D than in group B (P less than 0.05). The P62 level was reduced in group D compared with that in group B (P less than 0.05). In conclusion, GLP-1 intervention can change the proliferation and autophagy status of islet β cells in mice, and thus protect the function of islet β cells.