Protective effects of the injectable recombinant protein of exendin-4 and human serum albumin, E2HSA, on mouse islet β cell function
10.16438/j.0513-4870.2019-1062
- VernacularTitle:注射用重组艾塞那肽-人血清白蛋白融合蛋白E2HSA对小鼠胰岛β细胞功能的保护作用
- Author:
Cai-na LI
1
;
Shuai-nan LIU
1
;
Quan LIU
1
;
Yi HUAN
1
;
Su-juan SUN
1
;
Zhu-fang SHEN
1
Author Information
1. Diabetes Research Center of Chinses Academy of Medical Sciences, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
E2HSA;
islet β cell;
proliferation;
apoptosis;
alloxan-induced hyperglycemic mice
- From:
Acta Pharmaceutica Sinica
2020;55(6):1175-1181
- CountryChina
- Language:Chinese
-
Abstract:
The injectable recombinant protein of exendin-4 and human serum albumin (HSA), E2HSA, is a long-acting glucagon like-peptide-1 (GLP-1) receptor agonist, which is in clinical research stage now. This study aimed to evaluate the protective effects of E2HSA on mouse islet β cell function in vitro and in vivo. In vitro, the mouse insulinoma cells NIT-1 were used to assay the effects of E2HSA on cell viability and proliferation. Besides, the water soluble cholesterol was adopted to induce cell injury, and then the effects of E2HSA on cell viability and apoptosis, as well as the mechanism, were studied. In vivo, the alloxan-induced hyperglycemic mice were repeatedly administered with E2HSA by subcutaneous injection, and the blood glucose, serum insulin, and content of insulin in islets were measured. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). The results showed that E2HSA significantly increased the viability of NIT-1 cells and the amount of bromodeoxyuridine (BrdU) incorporated in cells. Besides, the water soluble cholesterol significantly decreased the cell viability and induced apoptosis of NIT-1 cells, but E2HSA significantly reversed the injury of NIT-1 cells. Nevertheless, E2HSA significantly increased the expression of pancreatic duodenal homeobox-1 (PDX-1) and protein kinase B (PKB) of NIT-1 cells after injured by water soluble cholesterol. Furthermore, repeated injections of E2HSA significantly reduced the fasting and non-fasting blood glucose, increased the serum insulin level and raised the insulin content in β cells of alloxan-induced hyperglycemic mice. In conclusion, E2HSA could promote proliferation of NIT-1 cells, inhibit the water soluble cholesterol induced injury and apoptosis, and increase the insulin content in serum and islets of alloxan-induced hyperglycemic mice, suggesting the protective effects on pancreatic islet β cell function.
