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Research progress of islet amyloid peptides

Amyloidosis of protein or polypeptide is caused by a variety of reasons, such as protein / polypeptide misfolding or structural changes, resulting in abnormal aggregation, and finally forming rich protein β- Lamellar fibrotic aggregates were deposited in the lesion. Protein amyloidosis is associated with a variety of diseases, such as Blzheimer, Parkinson's disease, diabetes and so on.

Keywords: Research Progress of islet amyloid protein diabetes mellitus

Diabetes is one of the major diseases that have not yet been conquered in the world. Type 2 diabetes is the main type of diabetes, which accounts for 90% of the total number of adults with diabetes. Because of the large number of patients and the lack of treatment, type 2 diabetes has attracted wide attention from scientists. With the deepening of the research in this field, human islet amyloid polypeptide (hIAPP) has entered people's field of vision and gradually attracted attention.

1. Synthesis of islet amyloid polypeptide

Islet amyloid polypeptide is encoded by the gene on chromosome 12, and it is obtained from 89 amino acids by a variety of enzymes. The polypeptide chain containing 89 amino acids cut off the signal peptide and became the precursor of islet amyloid polypeptide with 69 amino acid residues in the process of trans endoplasmic reticulum membrane transport. After that, 13 amino acids were cleaved from the N-terminal by PC2 to form an intermediate peptide with 56 amino acid residues. Then, 16 amino acids were cut off by PC1 / 3 to obtain an intermediate peptide with 40 amino acid residues. Next, carboxypeptidase-e removes lysine and arginine from the carbon terminal. Finally, the mature islet amyloid polypeptide was obtained by oxidation and amidation of the carbon terminal with glycidyl monooxygenase.

2.Biological function of islet amyloid peptide

Islet amyloid polypeptide is the coordinated chaperone of insulin, which is secreted by islet cells in a ratio of 1:100. IAPP has many unique physiological functions. It plays an important role in maintaining glucose homeostasis, controlling gastric emptying and inhibiting glucagon release. As a sign of obesity, IAPP is also involved in controlling satiety, thereby helping to reduce eating. Other studies suggest that IAPP can help regulate blood glucose level by inhibiting insulin secretion. In recent years, it has been found that islet amyloid polypeptide may be related to maternal effect. This is because it is up-regulated in front of the optic lobe of the hypothalamus in the early postpartum period.

3.Relationship between islet amyloid polypeptide 3 and type 2 diabetes mellitus

In type 2 diabetes, the resistance of target cells to insulin makes the islet secreting excessive insulin, resulting in over expression of islet amyloid polypeptide. In the study of islet amyloid precursor, scientists have found that it is associated with injury of type II diabetes and islet cells. It has been reported that the precursor of islet amyloid polypeptide initiates the aggregation process of islet amyloid polypeptide. Insulin resistance can cause excessive secretion of insulin peptide precursor and islet amyloid peptide precursor, and both of them need enzyme cleavage to produce insulin and islet amyloid peptide. However, in type 2 diabetes, the expression of the enzyme is not up-regulated, so in the unit time, there will be an excess of islet amyloid precursor in the body, resulting in the increase of the local protein concentration, resulting in the abnormal aggregation of the protein. In addition, the aggregation of islet amyloid polypeptide precursor provides a template for the aggregation of islet amyloid polypeptide, thus accelerating the aggregation of islet amyloid polypeptide.

4.Inhibitors of islet amyloid polypeptide aggregation

The reported aggregation inhibitors of hIAPP are mainly divided into the following categories: the first category is traditional small molecule inhibitors, most of which are natural products and contain aromatic groups. Studies have shown that aromatic groups can bind with phenylalanine of 20-29, the core hydrophobic segment of islet amyloid polypeptide, through π - π interaction to inhibit its further fibrosis aggregation. Another kind of common inhibitors is polypeptide inhibitors, which have good biocompatibility, high specificity and no immunogenicity; The third type of inhibitors are mainly nanomaterials, which have the characteristics of small size, large specific surface area and long retention time in vivo. At present, nanomaterials such as gold nanospheres, quantum dot nanoparticles, magnetic iron oxide nanoparticles, polymer nanoions and so on have been used to inhibit the aggregation of fibrosis.

5 Summary and Prospect

In this review, we summarize the synthesis and biological functions of islet amyloid peptide, the relationship between diabetes and islet amyloid polypeptide, and the inhibitors of amyloid peptide aggregation. As type II diabetes has become a worldwide high incidence disease, the number and type of drugs used for treating type 2 diabetes are increasing year by year. However, the actual performance of various drugs is far from achieving the best clinical results. A large number of studies have shown that oligomers and aggregation processes formed by hIAPP aggregation are the key factors to destroy the normal function of islet cells. Therefore, the development of inhibitors inhibiting hIAPP aggregation provides a new method for the treatment of type II diabetes.