The calcitonin gene-related peptide (CGRP, colored blue) and the related peptide, amylin (colored green), each has a total of 37 amino acids; see Figure 1A. Of the 37 amino acids of CGRP and amylin, 17 are colored gold, marking the identical amino acid positions in these two peptides.
Fig1. Amino acid sequences of calcitonin gene-related peptide (CGRP) and amylin. (A) The CGRP and the related peptide, amylin, are both members of the family of calcitonin-gene-related peptide and related peptides. Both peptides, CGRP and amylin, have 37 total amino acids. Of the 37 amino acids of CGRP and amylin, 17 (45%) are colored gold marking the identical amino acid positions in these two peptides. (B) Both peptides have a 6-amino acid ring structure created by the disulfide bond occurring between cysteine #2 and #7. Both peptides have a 6-amino acid ring structure created by the disulfide bond occurring between cysteine #2 and #7.
CGRP stimulates, in the pancreas, an 8× increase in amylase secretion. CGRP is primarily released from sensory nerves. This can then result in smooth muscle relaxation.
Amylin is cosecreted with insulin from the pancreatic β-cell. The insulin/amylin secreted ratio is ~100:1. Amylin plays a role in glycemic regulation by slowing gastric emptying and thereby increasing satiety. Amylin is also biosynthesized in the intestine, stomach, lung, and hypothalamus.
Amylin is related to the disease state of amyloidosis that shares in common the deposition of insoluble fibrillar proteins outside of cells. These are part of a growing group of diseases now thought to be caused by misfolding of proteins. It has been found that many amyloidoses have deposits that have a common β-pleated sheet structural conformation.
As shown in Figure 1B both peptides can form a 6-amino acid ring structure created by the disulfide bond occurring between cysteine #2 and cysteine #7. Human amylin carries out inappropriate formation of amyloids. Residues #22 to #29 are responsible for the formation of the amyloid fibrils. The amyloids are aggregates of a variety of insoluble proteins which arise from an inappropriate folding of the affected proteins. They also can have a deposit of common β-pleated sheets. Their presence has been associated with diseases because of the accumulation of amyloid fibriles in a variety of organs, including the pancreatic islets, which can lead to a variety (~20 versions) of neurodegenerative disorders.
