Immunoreactivity and Biologic Activity of Semisynthetic [Leu^B30]-Insulin: Potential Value in the Treatment of Insulin Antibody-Mediated Insulin Resistance

Insulin analogues with different amino acids, including threonine, alanine, L-leucine, D-leucine, L-leucine amide, phenylalanine, tri-alanine, or desalanine, at the B-30 position were semisynthesized from pork insulin by the new enzymatic method. The order of ability of the insulin analogues to bind to anti-insulin sera was [Ala^B−30] > desalanine > [Thr^B−30] > [Ala-Ala-Ala^B−30] > [D-Leu^B−30], [Leu-NH₂^B−30], [Phe^B−30] > desoctapep-tide > [Leu^B−30]. The ability of insulin analogues with different amino acids at B-30 to bind to receptors, as well as their biologic potency tested with glucose uptake in isolated rat adipocytes, was comparable among the analogues. These results suggest that [Leu^B−30]-insulin demonstrated the least immunoreactivity and has full activity in receptor binding and biologic effect, and that it may be useful for treatment of anti-insulin antibody-mediated insulin resistance.