糖尿病患者におけるインスリン-I<SUP>131</SUP>の血中動態に関する研究
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概要
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Regarding the altered metabolism of insulin in diabetics, the half time disappearance of insulin-I<SUP>131</SUP>, the distribution space of insulin-I<SUP>131</SUP>, the insulin binding index of serum and the disappearance of insulin-I<SUP>131</SUP> from the serum incubated with rat diaphragm (T1/2 in vitro) were studied with reference to the time and age of onset, the insulin requirements, the duration of insulin treatment, the presence or absence of diabetic nephropathy and retinopathy, the fasting blood sugar, the glucose assimilation coefficient and the insulin sensitivity index.<BR>Doses of 50-100 μc. of insulin-I<SUP>131</SUP> were administered intravenously to human subjects and heparinized blood samples were taken at intervals thereafter. Assays of radioactivity were carried out on plasma and precipitates of plasma treated with trichloraceticacid (TCA). Radioactivity precipitated by the modified two antibody technic of Morgan et al., using anti-insulin guinea pig serum and rabbit anti-guinea pig serum, was also assayed and the results were compared with the values obtained by TCA precipitation.<BR>In general, the curve of TCA precipitable radioactivity paralleled closely with that of radioactivity separated by the two antibody technics in each case, although the former was much flatter than the latter. In plasma from patients with marked insulin-binding antibody of their own, precipitation of radioactivity by the two antibody technics were incomplete.<BR>No significant differences in half time disappearance of insulin-I<SUP>131</SUP> could be observed between control subjects and diabetics never treated with insulin. In diabetics treated with insulin for a long time, the disappearance of insulin-I<SUP>131</SUP> from plasma was much slower than in diabetics who were never treated with insulin or treated with insulin for a short period. Insulin-I"' disappeared less rapidly from plasma in patients requiring a large dose of insulin, in juvenile-onset diabetics and in diabetics with retinopathy or nephropathy. Some correlation seemed to exist between the half time disappearance of insulin-I<SUP>131</SUP> and the insulin binding index of serum. The insulin-I<SUP>131</SUP> half time had little relation with the fasting glucose concentration in the blood, the glucose assimilation coefficient and the insulin sensitivity index.<BR>Insulin-I<SUP>131</SUP> distributed in a volume almost equal to the extracellular compartment in control subjects and diabetics who had never been treated with insulin, whereas in patients treated with insulin for a long time or requiring a large dose of insulin, the insulin-I<SUP>131</SUP> distribution space and the plasma volume were more nearly equal. A good relationship was found to exist between the insulin-I<SUP>131</SUP> distribution space and the insulin binding index of serum in diabetics.<BR>T1/2 in vitro was longer in diabetics than in non-diabetics, although it had nothing to do with either the half time disappearance in vivo or the insulin binding index of serum.<BR>In patients with diseases of the kidney, insulin-I<SUP>131</SUP> disappeared from plasma slower than in control subjects and the insulin-I<SUP>131</SUP> half time was inversely proportional to the value of the excretion of PSP in 120 minutes.<BR>In patients with diseases of the liver, the insulin-I<SUP>131</SUP> half time was slightly longer than in control subjects but there was no correlation between the insulin-I'3' half time and the value of the retention of BSP at 45 minutes.<BR>Rabbits immunized with beef insulin exhibited enhanced binding of insulin by serum and the insulin-I<SUP>131</SUP> distribution space in the immunized group was a tenth as small as in the control group, although the half time disappearance was only slightly longer in the immunized group than in the control group.
- 日本内分泌学会の論文