Establishment Of 3D Organ Chip For Multiplex Assessment Of Type 2 Diabetes Drugs

The incidence of type 2 diabetes in China has increased year by year,becoming a type of disease that seriously endangers people's health,but its specific pathogenesis is currently unclear.Lipopolysaccharide(LPS)is one of the main components of the cell wall of Gram-negative bacteria,and it is also the main pathogenic factor of Gram-negative bacteria.Both animal experiments and human studies have shown that LPS can activate immunity as an antigen.Systematic,LPS levels are elevated in patients with type 2 diabetes compared to non-diabetic individuals.Glucagon-like peptide(GLP-1)is a widely used class of hypoglycemic drugs.In addition to the classical hypoglycemic mechanism its anti-inflammatory effect is now receiving more and more attention.Can GLP-1 be used by exerting its anti-inflammatory effect,further regulation and improvement of islet ?-cell function the current research can not give a clear answer.Liraglutide is an analog of human glucagon-like peptide 1(GLP-1)that has been approved for the treatment of type 2 diabetes.In this paper,using the advantages of microfluidic chip in the operation and analysis of cells,a dual-channel hybrid microfluidic chip was designed,and a model of fat 3D organ chip,islet 3D organ chip and its joint application was established.The process of chronic inflammatory reaction caused by fat in the body,the cytokines secreted by the fat organs and lipopolysaccharide(LPS)are jointly introduced into the chip culture chamber of the islet organ,and the chip channel is continuously perfused to simulate body fluid exchange.By analyzing the secretion of inflammatory factors such as adiponectin(ADP),interleukin-6(IL-6)and interleukin-1?(IL-1?)in adipocytes and islet cells,and the insulin secretion ability of islet cells were compared with the control cells.Compare the changes produced,analyze the damage of islet cells and the inflammatory response in the system.The role of adipose tissue and LPS in the pathogenesis of type 2 diabetes and the role of liraglutide in improving insulin resistance were initially evaluated.It was found that LPS can cause inflammatory and functional changes in islet cells,and the presence of adipose tissue can aggravate this response to a certain extent;Liraglutide can alleviate LPS by reducing the inflammatory response of fat and islet cells.Adipose tissue stimulates islet cells to improve the function of islet cells.A platform for the combined use of a fat organ and a islet organ based on a microfluidic chip can be applied to a multi-organ disease response resulting from the interaction between different tissues.