Insulin is synthesized as a single polypeptide known as preproinsulin in pancreatic beta cells.
Preproinsulin harbours a 24-residue signal peptide, which directs the nascent polypeptide to the endoplasmic reticulum.
The signal peptide is cleaved as the polypeptide is translocated into the human of the endoplasmic reticulum resulting in the formation of proinsulin.
In the Endoplasmic reticulum, the
proinsulin is folded in proper confirmation with the formation
of 3 disulphide bonds. Folded proinsulin is then
transported to the trans-Golgi network, where it is
converted into active insulin by cellular endopeptidases
called as prohormone convertases (PC1 and PC2) and
exoprotease carboxypeptidase E. The endopeptidases
cleaves at two positions, resulting in the release of a fragment
termed as C-peptide. The mature insulin, thus
formed consists of an A-chain with 21 aminoacids and a
B-chain containing 30 aminoacids and both polypeptides
linked together by two disulphide bonds. Besides, the
A-chain has an intrachain disulphide bond [37,38].