Retinol Binding Protein 4 Impairs Pancreatic Beta-Cell Function, Leading to the Development of Type 2 Diabetes
DIABETES(2018)
摘要
Circulating Retinol binding protein 4 (RBP4), the specific transport protein for vitamin A, has been implicated in insulin resistance and type 2 diabetes. Pancreatic beta cell failure plays a decisive role in the onset and the progression of type 2 diabetes. However, the effect of RBP4 on beta cell function and the molecular mechanisms are far from clear. The direct effect of RBP4 on islet function was assessed by treating primary isolated islets from C57BL/J mice with different dose of RBP4 (0, 20, 40, 60 μg/ml) for 24 hour or with 60ug/ml RBP4 for different time points (0, 12, 18,24 hours). We found that RBP4 could dose and time dependently inhibit the glucose stimulated insulin secretion (GSIS). To further identify the role of RBP4 on islet beta cell function. RBP4-overexpressing mice (RBP4-Tg) were generated. Compared to the wild type group, the islets isolated from RBP4-Tg mice showed a significant decrease of insulin secretion in response to glucose (∼50%) and KCl (∼70%). The Dynamic insulin secretion of the isolated islets of RBP4-tg mice in response to glucose was further characterized. RBP4 could dramatically inhibit first-phase GSIS by up to 80%. In consistent to these in vitro findings, RBP4-tg mice showed a progressive decrease of GSIS (8weeks, 12weeks, 16weeks) which appeared as early as 8weeks. While the glucose tolerance of these mice was not significantly impaired until 12 weeks by intraperitoneal glucose tolerance test and the insulin sensitivity was not changed until 16 weeks by intraperitoneal insulin tolerance test respectively. In conclusion, RBP4 could impair pancreatic beta cell function which may lead to the onset and the development of T2DM. Disclosure R. Huang: None. X. Bai: None. X. Li: None. L. Zhao: None. M. Xia: None.
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关键词
diabetes,protein,beta-cell
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