GLP-1 (Glucagon-Like Peptide-1 Receptor) is a gastrointestinal hormone. Generally speaking, intestinal L cells produce GLP-1, which regulates blood glucose primarily via stimulation of glucose-dependent insulin release. In addition to insulin-releasing and appetite suppressant activity, GLP-1 also has direct insulin-like activity. That’s to say, GLP-1 has hypoglycemic effects.Specifically, studies have shown that GLP-1 has a glucose concentration-dependent hypoglycemic effect, inhibits gastrointestinal peristalsis and gastric juice secretion, inhibits appetite and ingestion, and delays gastric emptying. Here, we focus on the GLP-1 agonist, Exendin-4 (Exenatide).

Exendin-4 is a long-acting GLP-1 agonist. Notably, Exendin-4, a 39 amino acid peptide, is a long-acting GLP-1 receptor agonist with an IC₅₀ of 3.22 nM.

In vitro, Exendin-4 significantly increases NO production, endothelial NO synthase (eNOS) phosphorylation, and GTP cyclohydrolase 1 (GTPCH1) level in a dose-dependent manner. Alternatively, Exendin-4 shows cytotoxic effects to MCF-7 breast cancer cells with an IC₅₀ of 5 μM at 48 hour. In vivo, animals treated with Exendin-4 have more pancreatic acinar inflammation, more pyknotic nuclei and weigh significantly less than control rats. Furthermore, Exenatide causes dose-dependent relaxation of rat thoracic aorta. Consequently, these show that a central role for Exendin-4 in metabolic disorder models systems and the long-acting of Exendin-4. Interestingly, Exendin-4 treatment has some connection with lower leptin levels as well as lower HOMA values in rats. Moreover, both low- and high-dose Exendin-4 treatment in ob/ob mice improve serum ALT and reduce serum glucose, and calculated HOMA scores compared with control.

Taken together, Exendin-4 is a long-acting GLP-1 Agonist. To sum up, E67-2 is a potent compound of metabolic disorder research.

References：

[1]. Ding X, et al. Hepatology. 2006 Jan; 43(1):173-181.

[2]. Nachnani JS, et al. Diabetologia. 2010 Jan; 53(1):153-159.