Endothelial cells actively concentrate insulin during its transendothelial transport
Amanda J Genders1, Vera Frison, Sarah R Abramson
1Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA.
Objective:
We examined insulins uptake and transendothelial transport by endothelial cells in order to: (i) ascertain whether insulin accumulates within the cells to concentrations greater than in the media; (ii) compare trans endothelial insulin transport to that of inulin (using the latter as a tracer for passive transport or leaked); and; (iii) determine whether insulins transported depended on insulin action.
Methods:
Using 125I-insulin at physiologic concentrations we measured both the uptake and trans endothelial transport of insulin by bovine aortic endothelial cells and measured cell volume using tritiated 3-O-methylglucose.
Results:
Bovine aortic endothelial cells accumulate insulin to > five-fold above the media concentrations and the trans endothelial transport of insulin, but not inulin, is saturable and requires intact PI-3-kinase and MEK signaling.
Conclusion:
The insulin receptor and downstream signaling from the receptor regulates endothelial insulin transport. Insulin is accumulated against a concentration gradient by the endothelial cell. We suggest that insulin uptake is rate limiting for insulin trans endothelial transport.
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