Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin.
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Biomedical subjects
Publications and source records attributed to R Poucher.
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A 51-year-old, nonobese man with diabetes mellitus had marked hyperinsulinemia (70 to 120 muU per milliliter; 502 to 860 pmol per liter) and fasting hyperglycemia (140 to 170 mg per 100 ml; 7.8 to 9.4 mmol per liter). Plasma proinsulin, glucagon, growth hormone, and cortisol levels were normal; insulin antibodies and insulin-receptor antibodies were not detected. The patient showed relatively normal insulin sensitivity, and insulin receptors on circulating monocytes were within the normal range. Insulin from the patient's serum bound to IM-9 lymphocytes and rat adipocytes approximately 40 per cent as well as insulin standards. Its biologic activity on rat adipocytes averaged 15 per cent of that expected from its immunologic concentration. The impaired biologic activity of this patient's circulating insulin was probably due to a structural abnormality. Subsequent studies of the patient's insulin (fortuitously obtained from his pancreas during a laparotomy for a pancreatic cyst) have confirmed this conclusion. (N Engl J Med 302:129-135, 1980).
Insulin isolated from the pancreas of a diabetic patient with fasting hyperinsulinaemia showed decreased activity in binding to cell membrane insulin receptors and in stimulating cellular 2-deoxyglucose transport and glucose oxidation. Chemical studies suggest that the isolated hormone is a mixture of normal insulin and an abnormal variant which contains a leucine for phenylalanine substitution at position 24 or 25 of the insulin B-chain.
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