Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone convertases ( PC1 and PC2 ), as well as the exoprotease carboxypeptidase E .  The endopeptidases cleave at 2 positions, releasing a fragment called the C-peptide , and leaving 2 peptide chains, the B- and A- chains, linked by 2 disulfide bonds. The cleavage sites are each located after a pair of basic residues (lysine-64 and arginine-65, and arginine-31 and −32). After cleavage of the C-peptide, these 2 pairs of basic residues are removed by the carboxypeptidase.  The C-peptide is the central portion of proinsulin, and the primary sequence of proinsulin goes in the order "B-C-A" (the B and A chains were identified on the basis of mass and the C-peptide was discovered later).
In addition to insulin being considered a high-alert medication, insulin has also been known to be associated with more medication errors than most other medicines. The Institute for Safe Medication Practices performed a safety study on drug use in hospitals and found that 11% of all serious drug errors involved insulin misadministration. Another recent study at four . poison centers looked at calls taken over the past 10 years. They found that calls about insulin concerns have "skyrocketed." On average, the number of calls per year has almost tripled since 2002.
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