Human Amylin: From Pathology to Physiology and Pharmacology

• Published in: Current protein & peptide science Vol. 20; no. 9; p. 944
• Main Authors: Ling, Wei, Huang, Yan-Mei, Qiao, Yong-Chao, Zhang, Xiao-Xi, Zhao, Hai-Lu
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2019
• Subjects: Amyloid - metabolism; Amyloidosis - drug therapy; Amyloidosis - etiology; Amyloidosis - metabolism; Amyloidosis - pathology; Animals; Disease Susceptibility; Gene Expression Regulation; Humans; Islet Amyloid Polypeptide - chemistry; Islet Amyloid Polypeptide - genetics; Islet Amyloid Polypeptide - metabolism; Islet Amyloid Polypeptide - pharmacology; Islet Amyloid Polypeptide - therapeutic use; Protein Aggregation, Pathological; Signal Transduction; pramlintide; pathology; human amylin; Amyloid polypeptide (IAPP); pharmacology; insulinoma amyloid peptide
• ISSN: 1875-5550
• DOI: 10.2174/1389203720666190328111833

The histopathological hallmark of type 2 diabetes is islet amyloid implicated in the developing treatment options. The major component of human islet amyloid is 37 amino acid peptide known as amylin or islet amyloid polypeptide (IAPP). Amylin is an important hormone that is co-localized, copackaged, and co-secreted with insulin from islet β cells. Physiologically, amylin regulates glucose homeostasis by inhibiting insulin and glucagon secretion. Furthermore, amylin modulates satiety and inhibits gastric emptying via the central nervous system. Normally, human IAPP is soluble and natively unfolded in its monomeric state. Pathologically, human IAPP has a propensity to form oligomers and aggregate. The oligomers show misfolded α-helix conformation and can further convert themselves to β-sheet-rich fibrils as amyloid deposits. The pathological findings and physiological functions of amylin have led to the introduction of pramlintide, an amylin analog, for the treatment of diabetes. The history of amylin's discovery is a representative example of how a pathological finding can translate into physiological exploration and lead to pharmacological intervention. Understanding the importance of transitioning from pathology to physiology and pharmacology can provide novel insight into diabetes mellitus and Alzheimer's disease.