Insulin entry into muscle involves a saturable process in the vascular endothelium
S Majumdar1, A J Genders, A C Inyard
1University of Virginia Health System, PO Box 801410, 450 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
Diabetologia
|October 18, 2011
Summary
Insulin transport into skeletal muscle is a saturable process, likely involving the insulin receptor. This finding is crucial for understanding how muscle insulin action is regulated in various health conditions.
Area of Science:
- Endocrinology
- Physiology
- Molecular Biology
Background:
- Insulin's entry into skeletal muscle is key for its action and is impaired in insulin resistance.
- The mechanism of insulin transport into muscle interstitium is debated: passive diffusion versus receptor-mediated transport.
Purpose of the Study:
- To investigate whether insulin transport into skeletal muscle is a saturable process regulated by the insulin receptor.
- To determine the rate-limiting step in muscle insulin action.
Main Methods:
- Direct measurement of radio-labelled insulin uptake in rat hindlimb muscle.
- Assessment of insulin transport under conditions of high unlabelled insulin concentration (clamp and bolus).
- Use of mono-iodinated insulin and short exposure times to trace intact insulin.
Main Results:
- High concentrations of unlabelled insulin significantly reduced skeletal muscle insulin clearance.
- Insulin transport into liver, spleen, and heart was slowed, while kidney uptake increased.
- Electrical stimulation to increase muscle perfusion did not overcome the inhibitory effect of high insulin concentrations on muscle uptake.
Conclusions:
- Insulin transport across the muscle endothelium is a saturable process, likely mediated by the insulin receptor.
- Trans-endothelial insulin transport is a potential regulatory site for muscle insulin action in health and disease.
- Findings highlight the importance of insulin receptor-mediated transport in muscle insulin sensitivity.
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