Insulin internalization and intracellular protein degradation: a quantitative correlation

Area of Science:

• Biochemistry
• Cell Biology
• Endocrinology

Background:

• Insulin's action is known to involve intracellular processes.
• Internalization of insulin has been previously shown to be essential for its effects on intracellular proteolysis.

Purpose of the Study:

• To quantitatively investigate the relationship between the rate of insulin internalization and its ability to inhibit intracellular proteolysis.
• To determine the correlation between insulin internalization rate and its biological effects.

Main Methods:

• Utilized the acidification technique to differentiate surface-bound from internalized 125I-insulin.
• Calculated the rate of insulin internalization (K-e) using the internalized to surface-bound insulin ratio over time.
• Assessed insulin's effects on C14-glucose incorporation into glycogen and C14-valine labeled protein degradation.
• Investigated the impact of blocking insulin internalization with phenylarsine oxide.

Main Results:

• Insulin dose-dependently increased glucose incorporation into glycogen and inhibited intracellular protein degradation.
• Blocking insulin internalization with phenylarsine oxide diminished its effect on proteolysis but not on glucose incorporation.
• A direct significant correlation was found between the rate of insulin internalization (K-e) and the inhibition of intracellular proteolysis (r = .72, P < .05).
• A significant correlation also existed between the total amount of internalized insulin and the inhibition of intracellular proteolysis (r = .84, P < .01).

Conclusions:

• Insulin internalization is directly correlated with its ability to inhibit intracellular proteolysis.
• The rate of insulin internalization is a key determinant of its action on protein degradation.
• These findings reinforce the importance of insulin internalization for mediating its metabolic effects.