Endogenous insulin is derived from proinsulin, which is synthesised exclusively on the rough endoplasmic reticulum of pancreatic B cells (Fig. 20.14). Proinsulin is cleaved enzymatically in the b-granules of the B cells to form two peptides, insulin and C-peptide, both of which are released into the circulation following an insulinotrophic stimulus. Intracellular cleavage of proinsulin into the two peptides is usually almost complete and, consequently, very little proinsulin enters the circulation, even in response to intensive B-cell stimulation.
