How does exendin-4 work?

Exendin-4 is a 39–amino acid peptide that originally was isolated from the salivary secretions of the Gila monster lizard (11). It shares approximately 53% homology with the mammalian incretin GLP-1 and binds to and activates the mammalian receptor for GLP-1 cloned from pancreatic β cells (12,13).

How was exendin-4 discovered?

Exendin-4 is a short incretin-mimetic peptide consisting of 39 amino acids. It is discovered in the venom of Heloderma suspectum as a full agonist for the glucagon-like peptide 1 (GLP-1) receptor and produces insulinotropic effects.

How do glucagon-like peptides work?

Glucagon-like peptide 1 encourages the release of insulin from the pancreas, increases the volume of cells in the pancreas that produce insulin (beta cells) and holds back glucagon release.

What does GLP-1 do?

The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions.

Who discovered exendin 4?

Exendin-4 was uncovered in 1990 by endocrinologist Dr. John Eng at the Veterans Administration Center in the Bronx, NY.

What is the leading cause of death in diabetics?

Cardiovascular disease could be the most common cause of death in diabetic patients, followed by cancer.

Do Gila monsters have venom?

Gila monster venom is about as toxic as that of a western diamondback rattlesnake. However, a relatively small amount of venom is introduced in a Gila bite. Gila monsters may hold onto a predator for more than ten minutes. There is no antivenin for Gila bites.

How much do GLP-1 lower A1C?

GLP-1 RAs have effects on both fasting and prandial blood glucose levels. They are also associated with a significant potential to lower A1C. A head-to-head review of clinical studies determined that among available GLP-1 RAs, there were A1C reductions from 0.78% to 1.9%.

What class is Byetta?

Byetta belongs to a class of drugs called Antidiabetics, Glucagon-like Peptide-1 Agonists.

How does exendin 4 work in type 2 diabetes?

Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1). Exendin-4 is the active component of Byetta (exenatide) injection, which may improve glycemic control in people with type 2 diabetes mellitus and has the potential to reduce plasma glucose at least partly by a delay in gastric emptying as well as by reducing…

Which is a potent agonist of exendin-4?

Exendin-4 is a 39-amino acid peptide amide. Exendin-4, like Exendin-3, stimulates an increase in acinar cAMP without stimulating the release of amylase. Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1).

Why is exendin-4 less helical than GLP-1?

Exendin-4 has a helix-favoring glutamate as residue 16. In the micelle-associated state, NMR data indicate that GLP-1 is less helical than exendin-4 due to the presence of Gly16; chemical shift deviations along the peptide sequence suggest that Gly16 serves as an N-cap for a second, more persistent, helix.

What is the tertiary structure of exendin-4?

In aqueous fluoroalcohol or aqueous glycol, the Leu21-Pro38 span of exendin-4 forms a compact tertiary fold (the Trp-cage) which shields the side chain of Trp25 from solvent exposure and produces ring current shifts as large as 3 ppm. This tertiary structure is partially populated in water and fully populated in aqueous TFE.