Amylin Peptides

More about Islet amyloid polypeptide

Islet amyloid polypeptide (IAPP), also known as Amylin, is a 37 amino acid peptide co-secreted with insulin by the pancreatic beta cells; it contributes to glycemic control.

IAPP is a major constituent of protein deposits identified in the Islets of Langerhans of patients with noninsulin-dependent (Type-2) diabetes mellitus. These deposits mainly composed of ‘islet Amyloid’ are thought to contribute to pancreatic beta-cell dysfunction, either by direct cytotoxicity, apoptosis, or by reducing the beta-cell mass.

IAPP is processed from a 89-aa precursor, proIAPP. Islet amyloid formation seems to be initiated by the aggregation of proIAPP, which subsequently favors the aggregation of IAPP to form the amyloid islets.

The 20-29 fragment of human IAPP is critical to the pathogenesis of islet Amyloid, while the human IAPP fragment 22-27 [NMeG24, NMeI26] is a non-amyloidogenic and non-cytotoxic peptide. It is able to bind with high affinity to full-length hIAPP and to inhibit its fibrillogenesis effect.

Unlike the human IAPP, rat IAPP -which differs by 6 amino acids- does not seem to form amyloid fibers. Substitutions are H18R, F23L, A25P, I26V, S28P and S29P (first letter is the amino acid of the human sequence).

Pramlintide is a synthetic amylin analogue drug for diabetes (both type 1 and 2), with Proline residues at positions 25, 28, and 29 (similar to the rat sequence).

References

• Kahn, SE. et al. Diabetes l. 48, 241 (1999)
• Bennett, R. et al. J. Biol. Chem. 275, 36621 (2000)
• Edelman S. et al. BioDrugs 22(6):375-86 (2008)