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发表时间：2019-01-01

发表刊物：生物化学与生物物理进展

卷号：46

期号：06

页面范围：620-630

ISSN号：1000-3282

摘要：Type 2 diabetes is a systematic metabolic disease that involves complex interplay of multiple organs, of which adipose tissue and pancreatic islet are two key organs related to its pathogenesis. In this paper, models of fat 3D organ chip, islet 3D organ chip and their combination were established, which can be used to study the pathogenesis and to assess the mechanism of hypoglycemic agents for treatment of type 2 diabetes. A two-channel composite microfluidic chip was designed to study the effects of lipopolysaccharide (LPS) first on fat cells in one chip chamber and on islet cell in a seperate chip culture chamber. The chip channel was continuously perfused to simulate constantly changes in contents of the body fluid. The secretion of inflammatory factors such as adiponectin (ADP), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) from adipocytes and islet cells, the insulin secretion from islet cells, and islet cell survival rate in medium flashed with LPS or LPS / liraglutide were compared with those from cells flashed with the control medium. The results showed that LPS decreased ADP production from fat 3D organ chip, in islet 3D organ chip, and in fat/islet 3D double organ chip, LPS promoted IL-1 beta and IL-6 production from fat 3D organ chip and 3D fat/islet double organ chip, but not from islet 3D organ chip. Liraglutide could improve the production of ADP, and decreased IL-1 beta, IL-6 from fat 3D organ chip and fat/ islet 3D double organ chip, but no effects on islet 3D organ chip. LPS and liraglutide separate or in combination had no effect on insulin production from islet 3D organ chip, but LPS decreased insulin production from fat/islet 3D double organ chip, liraglutide improved the decreased insulin production from fat/islet double organ chip due to LPS. The platform for the combined application of the fat organ and the islet organ based on the microfluidic chip can be applied to the multi-organ disease reaction caused by the interaction between different tissues and is expected to be a powerful tool for drug evaluation of systemic metabolic diseases such as type 2 diabetes.

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