AMYLIN, HUMAN

Description

Amylin is a 37-peptide that is structurally similar to CT. Amylin works together with insulin to regulate glucose concentrations after a meal. When in solution, amylin is viscous, unstable, and tends to aggregate; therefore it cannot be used parenterally and is not commercially available.

The Uses of AMYLIN, HUMAN

Antidiabetic.

The Uses of AMYLIN, HUMAN

Amylin functions as part of the?endocrine?pancreas?and contributes to?glycemic control. It functions as a synergistic partner to insulin. The overall effect is to slow the rate of appearance (Ra) of glucose in the blood after eating.

Biochem/physiol Actions

Islet amyloid polypeptide (IAPP) is a hormone coexpressed with insulin by pancreatic β-cells. IAPP is used to study the mechanisms of amyloid deposition and its role in molecular misfolding processes expecially in conditions such as diabetes type II.

Clinical Use

Amylin normally is cosecreted with insulin from secretory granules in pancreatic β cells in response to meals and works with insulin to provide postprandial glucose control. Native amylin is a single-chain peptide of 37 amino acids. Observed deficiencies of amylin in both type 1 and type 2 patients treated with insulin have led to research and drug development related to amylin.

Clinical Use

Pramlintide, whose sequence is based on rat AMY to avoid amyloid formation, is used for the treatment of type 1 and type 2 diabetes to reduce blood glucose levels.

Storage

Store at -20°C

Structure and conformation

Human AMY is derived after a 67-aa residue proAMY. The short C- and N-terminal flanking peptides are cleaved by the prohormone convertases PC2 and PC1/3 to form the 37-aa residues of mature AMY. Human AMY20–29 is considered to be the responsive region that forms the amyloid fibrils in type 2 diabetes, as synthesized 20–29 aa residues are extremely fibrillogenic. However, rat and mouse models of diabetes lack the islet amyloid. The AMY20–29 regions vary among humans and rodents, and rat/mouse AMY has three proline residues, known as β-sheet breakers, in this region. Because the amyloid is the aggregated protein in which molecules in a β-sheet structure are bound to each other, the lack of the islet amyloid in rodents appears to be due to the presence of proline residues in the AMY20–29 region. Therefore, the peptides in these species are saved from fibrillogenic conformation. The sequence of mature AMY is highly conserved across vertebrate lineages, but the sequence at the position 20–29 regions is variable, which also supports the theory that the islet amyloid is observed only in humans and cats.