The effects of low temperature and chloroquine on 125I-insulin degradation by the perfused rat liver |
| |
Authors: | Patricia A Dennis Nathan N Aronson |
| |
Institution: | Program in Biochemistry, Althouse Laboratory, The Pennsylvania State University, University Park, Pennsylvania 16802 U.S.A. |
| |
Abstract: | Low temperature and the lysosomotropic agent, chloroquine, were used to study the degradation of 125I-insulin in a perfused rat liver. Insulin (1.5 × 10?9m) was removed from the perfusate at 35 °C with a of 12 min, and this process was slowed to 35 min at a temperature of 17 °C. Essentially no degradation of 125I-insulin took place in the liver at 17 °C. After 90 min at that temperature 64% of the liver radioactivity had accumulated in the microsomal fraction of the tissue homogenate, while at 35 °C 60% of the radioactive material was in the supernatant fraction. Greater than 80% of the supernatant radioactivity was acid soluble. Rapid warming of a 17 °C-treated liver to 35 °C allowed the accumulated 125I-insulin in the microsomal fraction to be degraded to acid-soluble products in the normal manner. Chloroquine (0.2 mm) also caused the liver to degrade insulin more slowly. At 60 min after adding 125I-insulin to the chloroquine-treated liver, 50% of the radioactivity in the tissue was still present in the lysosome-rich fraction of the homogenate, while less than 10% was in this fraction in a control liver. The effects of low temperature show transfer of insulin to its degradative site is rate limiting for hormone catabolism and the inhibition by chloroquine suggests lysosomes have a role in insulin degradation by the liver. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|