Peptidylglycine amidating monooxygenase
11 amino acids are removed from the N-terminus by the enzyme proprotein convertase 2 (PC2) while 16 are removed from the C-terminus of the pro IAPP molecule by proprotein convertase 1/3 (PC1/3).
The terminal glycine amino acid that results from this cleavage allows the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to add an amine group.
Proislet amyloid polypeptide (pro IAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 amino acid, 7404 Dalton pro-peptide and undergoes post-translational modifications including protease cleavage to produce amylin.
Pro IAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence.
Thus blood glucose levels play an important role in regulation of pro IAPP synthesis.
Amylin functions as part of the endocrine pancreas and contributes to glycemic control.
Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.
Once released from the signal peptide, it undergoes additional proteolysis and posttranslational modification (indicated by ^).
It is thought that pro IAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid-induced apoptosis of β-cells. Insulin resistance in Type 2 diabetes produces a greater demand for insulin production which results in the secretion of proinsulin.
Pro IAPP is secreted simultaneously, however, the enzymes that convert these precursor molecules into insulin and IAPP, respectively, are not able to keep up with the high levels of secretion, ultimately leading to the accumulation of pro IAPP.
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It is cosecreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1.