Influence of Short-Term Insulin Therapy on the Mesangial Structure in Young KK Mice

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Abstract
The influence of consistent normalization of the metabolism by insulin therapy on the glomerular structure in diabetes mellitus has, thus far, not been adequately elucidated. We studied this question by treating KK mice with genetic diabetes with immunologically inactive insulin (MC insulin) and an immunologically active insulin preparation (depot insulin). The kidneys from a total of 42 KK mice (6 weeks old) were studied, part of which remained untreated. We determined the number of glomerular cells and the glomerular and mesangial area using morphometric methods. Blood sugar level, proteinuria and insulin antibody titer were also determined. Treatment was carried out over a period of 12 weeks. As compared with the untreated animals, it was found that progression of the glomerular changes (mesangial cell proliferation, enlargement of the mesangium) does not occur if the animals are treated with immunologically inactive MC insulin (no antibody formation). On the other hand, treatment with immunogenic insulin (depot insulin) results in a rapid increase in the glomerular alterations and, in the course of time, the same changes are apparent as in the untreated control animals. The investigations show that accurate management of the metabolism (normalization of the blood sugar) by insulin, without concurrent antibody formation, leads to a marked improvement of the glomerular lesions.

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