The effect of iodination of particular tyrosine residues on the hormonal activity of insulin

Abstract

Insulin dissolved in aqueous or methanolic buffer was iodinated to give preparations containing an average of between one and five iodine atoms per insulin monomer. The resultant preparations were fragmented in various ways and the ratio of tyrosine to monoiodotyrosine and di-iodotyrosine was determined in each fragment. This has allowed the distribution of iodine between the combined A-chain tyrosine residues and the individual B-chain tyrosine residues to be determined. The hormonal activity of each of these iodinated insulin preparations was measured from their effect on the production of (14)CO(2) from [1-(14)C]glucose by isolated adipose cells. The results were interpreted as meaning that the iodination of tyrosine residue A19 or B16 leads to the inactivation of insulin. Speculations are made about the nature of an interaction between insulin and a receptor site on the target tissue.

B1-3,5-diiodotyrosine insulin: A valid tracer for insulin

“…However others have found purified monoiodoinsulins to be only partially active [26][27][28] or completely inactive [29]. The biological activities of some of these monoiodoinsulin preparations [26,27,29] correlated directly with the percentage of their radioactivit~r in the A14 position, consistent with the observation by Garratt et al [30] that iodination of A19 resulted in a reduced activity of the hormone. However the preparation of Linde and Hansen [28] showed the reverse trend.…”

Preparation and properties of (monoiodotyrosine)-insulin

“…lodinated insulins have found widespread use in radioimmunoassay and as biological tracers (Haugaard et al, 1954;Berson et al, 1956;Welsh et al, 1956;Edelman & Schwartz, 1966;Tomasi et al, 1967). Consequently, biological and immunological properties of iodinated insulins have been the subject of considerable investigation (De Zoeten & Van Strik, 1961;Izzo et al, 1964;Rosa et al, 1967;Glover et al, 1967;Arquilla et al, 1968;Brunfeldt et al, 1968;Massaglia et al, 1969;Freychet et al, 1971b;Garratt et al, 1972). Previous studies have been hampered by the lack of adequate separation techniques for the preparation of iodinated insulins.…”