The Hypoglycemic Effect Of Water Soluble Chitosan And The Studying Of Its Mechanism

Diabetes mellitus is one of the most common endocrine metabolic disorders. There are two types of diabetes, type 1 diabetes and type 2 diabetes. Type 1 diabetes which is also called autoimmune diabetes, results from selective destruction of the insulin-producingβcells in the pancreatic islets by immune cells. The mechanism of type 2 diabetes is insulin resistance.Although the incidence of type 1 diabetes is not very high, it is closely related to immunologic derangement. So, the research of type 1 diabetes can promote the development of immunology.Water Soluble Chitosan(WSC) which is derived from the partial deacetylation of chitin, is the only catnic polysaccharide in nature, it exhibits many particular phys chem properties and bioactivities. In previous, WSC has been found it had the effect of enhancing immune responses, for example, activiting resident macrophage. But in current research, we found that WSC also played an important role in curing wound healing and inflammation diseases like trachitis, indicting WSC could also attenuate stimulated macrophage.Macrophage plays an important role in the development of type 1 diabetes. At the early stages of autoimmune diabetes, macrophages, which are stimulated, secrete high levels of IL-6, and TNF-α. As a result, they kill pancreaseβcells.So, in this thesis, I am going to find whether WSC can cure autoimmune diabetes by attenuating stimulated pancreatic macrophage.First, studyed the basic characteristics of WSC by Atomic Force Microscope.The result showed that the configuration of WSC is bostrychoid.Second, studyed the hypoglycemic effect of WSC in vivo.We induced type 1 diabetic mice model by the method of multiple low-dose of streptozotocin (MLD-STZ). We cured them by WSC and the Levels of blood glucose, serum insulin, were separately calculated in normal group, type 1 diabetic mice group, and WSC curing group. The experiment showed that WSC could markdly reduce the levels of blood glucose; and increase the levels of insulin.Third, studyed the effect of WSC in attenuating stimulated macrophage.Different concentration of WSC were added to LPS stimulated macrophage. The expression of IL-6-mRNA, TNF-α-mRNA, and iNOS-mRNA were detected by RT-PCR. Results showed that compared to LPS group, WSC could decrease the expression of inflammatory factors.Fourth, studyed whether WSC could reduce inflammation of islets by regulating stimulated pancreatic macrophage in vitro.Different concentration of WSC were added to primary culture pancreaseβcell which was Co-cultured with LPS-stimulated macrophage. The level of NO, insulin were measured. Results showed that WSC could decrease the level of NO, but, increase the secretion of insulin.In summary, WSC lowered blood glucose in the type 1 diabetic mice, attenuated LPS stimulated macrophage, and cured pancreseβcells which are damaged by stimulated macrophage. Chitosan which is a natual product may be a novel drug to cure diabetes.