Yukio Yoshimura

Carbamylation of Insulin and Its Biological Activity

A nonspecific binding reaction between cyanic acid formed from urea and protein or peptide is called carbamylation. In the present study, insulin, a peptide hormone, was subjected to carbamylation and the activity of carbamylated insulin was determined. Both immunological and biological activities of insulin changed on carbamylation. The decrease in biological activity in respect to glucose oxidation of fat cells or receptor-binding capacity of rat hepatocytes was greater than that in immunological activity.

Carbamylation of hemoglobin in renal failure and clinical aspects.

It was revealed that in renal failure hemoglobin A1 (HbA1) was formed by the binding of substances other than glucose to Hb. It was elucidated that the formation of HbA1 increased in urea-added medium and further increased in media containing urea either stored at 37 degrees C for 1 week or heated at 100 degrees C for five minutes. The increment of HbA1 was proportional to the amount of cyanic acid produced by the treatment of the medium after the addition of urea. We found that there was the best correlation between the HbA1 level and the BUN level of 1 to 2 weeks before. Therefore, it appeared that HbA1 could be an indicator of the state of renal failure of 1 to 2 weeks earlier in patients with renal failure without impaired glucose tolerance, especially in patients on hemodialysis.

Determination of carbamylated plasma protein and its clinical application to renal failure.

We determined carbamylated plasma protein (CPP) according to the method of Hunninghake in patients with renal failure and normal subjects. CPP values were significantly higher in patients with renal failure than in normal subjects. In patients with renal failure, a significant correlation was found between CPP levels and blood urea nitrogen. Thus, CPP appears to be a new indicator of the status of renal failure, irrespective of hemodialysis.

Effects of glycosylation on physiological and biological activities of substances

Hemoglobin A1 (HbA1) increases in old erythrocytes. These erythrocytes with increased HbA1 had decreased oxygen dissociation ability, resulting in decreased function. L-Triiodothyronine (T3) underwent glycosylation to form glycosylated T3. The biological activity of glycosylated T3 was assayed utilizing the metamorphosis of tadpoles. It was found that glycosylated T3 was less than one-tenth as biologically active as T3.