Exendins and Fragments

Exendins is a peptide found in saliva secretions from Gila monsters and Mexican bearded lizards, native reptiles from Arizona and northern Mexico. Exendin-3 is found in the saliva secretions of Ganoderma lucidum (Mexican beaded lizard), and Exendin-4 is found in the saliva secretions of Heloderm Susputectom1 (Gila Monster). Exendins has certain homology with several members of glucagon-like peptide family, the highest homology is 53%. The histidine residue (His1) peptide Exendin-4 of 39 amino acid residues was isolated from the suspension by amino acid sequence analysis. Unlike Exendin-3, Exendin-4 has two amino acid substitutes. Gly2-Glu3 replaces Ser2-AsP3, but is the same in other ways. The difference of structure makes the biological activity of exendin-4 and exendin-3 different.

Mode of Action

Exendin-4 is a peptide amide composed of 39 amino acids. Exendin-4, like Exendin-3, stimulates the increase of acinar cAMP without stimulating amylase release. Exendin-4 is a long-acting agonist of glucagon-like peptide 1 (GLP-1). Exendin-4, an active ingredient of Byetta (Exenatide) injection, can improve blood glucose control in patients with type Ⅱ diabetes, at least by delaying gastric emptying and reducing calorie intake. Exendin-4 can promote glucose-dependent insulin secretion of pancreatic β cells and inhibit the inappropriate increase of glucagon secretion. Exendin-3 is a potent and selecive GLP-1 receptor antagonist. Exendin-3 (9-39) inhibits insulin release and cAMP production caused by GLP-1 (7-36), exendin-3, and exendin-4. Exendin-3 (9-39) also negates the inhibitory effect of GLP-1 on food intake in rats.

Function

Novel Exendin and exendin agonists have exendin or exendin agonists associated with one or more polyethylene glycol polymers, as well as related products and methods, For example, in the treatment of diabetes, including type Ⅰ, type Ⅱ and gestational diabetes and in the treatment of disorders which would be benefited by agents which modulate plasma glucose levels or suppress glucagon secretion. We can benefit from the use of drugs that benefit from regulating gastric emptying or food intake rates, including obesity, eating disorders, insulin resistance syndrome and triglyceride levels, as well as the treatment of dyslipidemia. These methods are also useful for reducing blood lipid levels, reducing heart risk, reducing appetite and reducing weight.

References

1. Liao, S., Liang, Y., Zhang, Z., Li, J., Wang, J., Wang, X., ... & Liu, K. (2015). In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PloS one, 10(2), e0116805.
2. Eng, J., Kleinman, W. A., Singh, L., Singh, G., & Raufman, J. P. (1992). Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. Journal of Biological Chemistry, 267(11), 7402-7405.