Abstract
Background
While the role of insulin in glucose uptake and its aberration in diabetes are well
established, the effect of insulin on lipoprotein clearance in the postprandial phase
is not yet fully understood. The dietary lipids are carried in chylomicron remnants
(CR) which are taken up into the liver mainly via LDLR-related protein 1 (LRP1). In
this study, the effect of insulin on LRP1-mediated hepatic CR uptake was investigated.
Methods
The study was based on determining the subcellular localisation of LRP1 by subcellular
fractionation and immunofluorescence microscopy and correlating those findings with
the hepatic uptake of fluorescently or radioactively labelled LRP1-specific ligands
and CR in hepatoma cells, primary hepatocytes and mouse models.
Results and conclusion
In vitro and in vivo, insulin stimulated the translocation of hepatic LRP1 from intracellular vesicles
to the plasma membrane, which correlates with an increased uptake of LRP1-specific
ligands. In wild-type mice, a glucose-induced insulin response increased the hepatic
uptake of LRP1 ligands while in leptin-deficient obese mice (ob/ob), which are characterised by hepatic insulin resistance, insulin-inducible LRP1 ligand
uptake was abolished. Finally, upon hepatic LRP1 knockdown, insulin no longer significantly
enhanced CR uptake into the liver. The insulin-induced LRP1-mediated CR uptake, as
demonstrated here, suggests that impaired hepatic LRP1 translocation can contribute
to the postprandial lipaemia in insulin resistance.
Keywords
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Article Info
Publication History
Published online: October 03, 2008
Accepted:
July 30,
2008
Received in revised form:
July 28,
2008
Received:
June 20,
2008
Identification
Copyright
© 2008 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
