Insulin Immunoassays: Fast Approaching 50 Years of Existence and Still Calling for Standardization

Insulin (51 amino acids, 5808 Da) is synthesized from its precursors preproinsulin and proinsulin (hPI; 86 amino acids) in the β cells of the pancreatic islets of Langerhans. A human insulin molecule is chemically homogeneous, consisting of 2 polypeptide chains, the A chain (21 amino acids) and B chain (30 amino acids), connected by 2 disulfide bonds (A7-B7 and A20-B19); a 3rd disulfide bond links the A6 and A11 residues. In serum, insulin circulates in a free form (not bound to carrier proteins) together with small quantities of its precursors, mainly intact hPI and des (31,32) split hPI (hPI cleaved at the junction between the B chain and C-peptide linking the A and B chains in the hPI molecule). Des (64,65) split hPI (hPI cleaved at the junction between the A chain and C-peptide) is a minor component of hPIs in serum (1). Insulin is the only hypoglycemic hormone. Its measurement in serum plays a central role in the assessment of β-cell secretion and insulin resistance. Ideally, an insulin assay should be sensitive, specific, and applicable to a large number of samples. It should also be standardized to be efficiently used in large multicenter clinical studies and considered in guidelines.