Immunoreactivity of Insulin Antibodies in Insulin-treated Diabetics: Significance of the Beta-chain Carboxyterminal Amino Acid (B-30) of Insulin

Abstract

We investigated the immunoreactivity of the carboxyterminal amino acid residue of the beta-chain of insulin using sera from 22 insulin-resistant and 51 nonresistant diabetic patients. We used three insulins, human, porcine, and desalaninated porcine, which differ only at the B-30 amino acid residue. The binding of 125I-human and 125I-desalanine porcine insulins with antibodies was reduced compared with that of 125lporcine insulin. Two-thirds of the insulin-resistant sera differentiated porcine and desalanine porcine insulins and had lower avidities for the latter. Most of these sera had lower affinities for human insulin compared with other insulins. The antibodies that bind with 125I-desalanine porcine insulin showed equal avidities for the human and unmodified porcine insulins. Five insulin-resistant patients had been treated with the commercial desalanine (dalanated) porcine insulin. One had a prompt reduction in insulin requirements, and three others needed reduced maintenance dosages. Sera of these four cases, but not of the nonresponder, had lower avidities for desalanine porcine insulin compared with porcine insulin. These observations indicate that the amino acid alanine at the B-30 position in the insulin molecule can influence the immunoreactivity of insulin antibodies in human sera, and may be a potential immune determinant.