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Editorials |
Institut de Physique Biologique, 1 place de lHôpital, F-67091 Strasbourg Cedex, France, Fax 33-3-90-24-40-57, e-mail remy.sapin@chru-strasbourg.fr
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Insulin (51 amino acids, 5808 Da) is synthesized from its precursors preproinsulin and proinsulin (hPI; 86 amino acids) in the ß 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 ß-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.
Among insulin assay methods, only immunoassays are applicable to large numbers of samples. The 1st RIA for human insulin, described in 1959 by Yalow and Berson (2), relied on competitive binding of human insulin in plasma samples or calibrators and 131I-labeled bovine insulin to guinea-pig antibovine insulin polyclonal antibodies. Separation of the bound and free fractions was performed by chromatoelectrophoresis. Later the availability of human insulin in larger quantities (3) allowed the production of guinea-pig antihuman insulin antibodies, and an antibody precipitation technique made the assay easier to use. Except for 1 assay, RIAs
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