Abstract
Amylin, (or islet amyloid polypeptide; IAPP), a 37-amino acid peptide hormone, is released in response to nutrients, including glucose, lipids or amino acids. Amylin is co-stored and co-secreted with insulin by pancreatic islet β-cells. Amylin inhibits food intake, delays gastric emptying, and decreases blood glucose levels, leading to the reduction of body weight. Therefore, amylin as well as insulin play important roles in controlling the level of blood glucose. However, human amylin aggregates and human amylin oligomers cause membrane disruption, endoplasmic reticulum (ER) stress and mitochondrial damage. Since cytotoxicity of human amylin oligomers to pancreatic islet β-cells can lead to diabetes, the protection of pancreatic islet β cells from cytotoxic amylin is crucial. Human amylin oligomers also inhibit autophagy, although autophagy can function to remove amylin aggregates and damaged organelles. Small molecules, including β-sheet breaker peptides, chemical chaperones, and foldamers, inhibit and disaggregate amyloid formed by human amylin, suggesting the possible use of these small molecules in the treatment of diabetes. In this review, we summarize recent findings regarding the role and cytotoxicity of amylin and the protection of pancreatic islet β-cells from cytotoxicity of amylin.
Highlights
Amylin, known as islet amyloid polypeptide (IAPP), is a 37-amino acid peptide hormone.Amylin is released in response to nutrients, including glucose, lipids, or amino acid [1,2].Pancreatic islets include α, β, δ, γ/pancreatic polypeptide (PP), and ε cells. α cells secrete glucagon, β-cells secrete insulin and amylin, δ cells secrete somatostatin, γ/PP cells secrete pancreatic polypeptide, and ε cells secrete ghrelin [3,4]
Pro-amylin is processed by prohormone convertase (PC) 1/3 and PC2, and its C-terminus is amidated by carboxypeptidase E and peptidylglycine alpha-amidating monooxygenase
CTR-like receptor (CLR) leadsofto the formation of different proteins receptors for calctionin, CGRPs, amylin and Combination activity-modifying (RAMPs) andand calcitonin receptor (CTR)
Summary
Known as islet amyloid polypeptide (IAPP), is a 37-amino acid peptide hormone. Amylin is a member of the calcitonin (CT) family, which includes CT, αcalcitonin gene-related peptide (αCGRP), βCGRP, adrenomedullin (AM), and AM2 ( known as intermedin). The members of this family comprise a disulfide bond at the N-terminus and an amidated C-terminus. Receptor activity-modifying proteins (RAMPs) are associated with CTR or CLR. CLR leadsofto the formation of different proteins receptors for calctionin, CGRPs, amylin and Combination activity-modifying andand calcitonin receptor CLR leads to the formation of different receptors for calctionin, CGRPs, amylin and adrenomedullins. (CT), αcalcitonin peptide or CLR leads to the formation of different receptors forcalcitonin calctionin, CGRPs, amylingene-related and adrenomedullins. Numerous proteins, including human amylin, aggregate and form amyloids. Human amylin forms amyloid fibrils, which are associated with damage to pancreatic islet β-cells and development of T2D [22]
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