Studies on monocomponent insulin. IV. Subcutaneous absorption of insulin from preparations with protracted action.

Abstract

Since purity and source species might influence the absorption of a long-acting monocomponent insulin (MC-insulin) preparation, studies were carried out with a preparation of mixed bovine and porcine insulin obtained by conventional recrystallization, a specially prepared preparation of mixed MC grade bovine and porcine insulin, a specially prepared preparation composed of recrystallized porcine insulin alone, and MC-insulin. These were injected subcutaneously into rabbits, and their absorption were examined using hypoglycemia as an index. The preparation composed only of porcine insulin gave a higher maximum hypoglycemic rate than the mixed bovine and porcine insulin preparation, but the blood glucose recovered to the original level earlier, indicating its more rapid absorption. This phenomenon was more strinking at larger test doses. However, there was no difference in absorption between preparations of different purity. Furthermore, the mixed MC-grade bovine and porcine insulin preparation and MC-insulin were subcutaneously administered to an in situ animal experimental model to determine the blood insulin course. MC-insulin was again found to be absorbed more rapidly. It is suggested that this occurs because porcine insulin crystals dissolve more rapidly than bovine insulin crystals. Such a difference in the solubility of the insulin crystals may be caused by configurational differences between porcine and bovine insulin, arising from the differences in the amino acid residues at positions 8 and 10 of the A-chain.