Insulin Binding and Degradation in Liver of Fed and Fasted Rats : Effect of Antiserum to Insulin-degrading Enzyme on Insulin Binding and Degradation

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概要

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• Kinetic studies on <SUP>125</SUP>I-insulin binding and degradation were examined using liver plasma membrane and cytosol fractions from fed and fasted rats.<BR>Liver plasma membranes of 72h fasted rats bound twice as much insulin as did membranes of fed rats. Scatchard analysis showed that the enhancement of <SUP>125</SUP>I-insulin binding in fasted rats was due to an increase of insulin receptor concentrations in the membranes. Specific activity of insulin degradation by plasma membranes was about 10% of the activity by the cytosol fraction and showed no significant difference between fed and fasted rats. On the other hand, insulin-degrading activity in the cytosol fraction from fasted rats was significantly lower than fed rats (P<0.02). Quantitative analysis of insulin degradation in the cytosol fraction revealed a similar Km for both groups (1.8 to 2.5×10<SUP>-7</SUP>M), while the maximal velocity (V<SUB>max</SUB>) in fasted rats was significantly lower than that of fed rats (P<0.02).<BR>The antiserum to insulin-degrading enzyme (IDE) purified from pig skeletal muscle was able to remove insulin-degrading activity in both the cytosol (34±7 vs 79±3% of the control, P<0.001) and plasma membrane fractions (49±7 vs 81±6% of control, P<0.01) by immunoprecipitation when compared with normal rabbit serum. Furthermore, <SUP>125</SUP>Iinsulin binding to plasma membranes significantly increased in the presence of the antiserum (121±9% of control, P<0.05).<BR>These data suggest that the number of insulin receptors in the plasma membrane increases, whereas the content of insulin-degrading enzyme (s) in the cytosol fraction decreases in the hypoinsulinemic state. Since insulin-degrading activity in plasma membranes does not change in the fasted state, insulin seems to be mainly degraded by intracellular enzyme (s) including IDE rather than the insulin-degrading system of plasma membranes in the rat liver.

• 社団法人 日本内分泌学会の論文

著者

• BABA SHIGEAKI

  Second Department of Internal Medicine, Kobe University School of Medicine

• YOKONO KOICHI

  Second Department of Internal Medicine, Kobe University School of Medicine

• IMAMURA YOSHIMICHI

  Second Department of Internal Medicine, Kobe University School of Medicine

• SHII KOZUI

  Second Department of Internal Medicine, Kobe University School of Medicine

• SAKAI HIDEYO

  Second Department of Internal Medicine, Kobe University School of Medicine

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