Journal
JOURNAL OF LIPID RESEARCH
Volume 54, Issue 5, Pages 1275-1282Publisher
ELSEVIER
DOI: 10.1194/jlr.M032904
Keywords
muscle fiber; GLUT4 transporter; diabetes; insulin resistance; apolipoprotein A-I; high density lipoprotein
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Funding
- Swedish Research Council [522-2008-3724, 7480]
- Crafoord foundation
- Albert Pahlsson foundation
- Gyllenstierna Krapperup's foundation
- Petrus and Augusta Hedlund foundation
- Jeansson foundation
- Ake Wiberg foundation
- Golje Foundation
- Swedish Society for Medical Research
- Wenner-Gren Foundations
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Lipid-free apoA-I and mature spherical HDL have been shown to induce glucose uptake in skeletal muscle. To exploit apoA-I and HDL states for diabetes therapy, further understanding of interaction between muscle and apoA-I is required. This study has examined whether nascent discoidal HDL, in which apoA-I attains a different conformation from mature HDL and lipid-free states, could induce muscle glucose uptake and whether a specific domain of apoA-I can mediate this effect. Using L6 myotubes stimulated with synthetic reconstituted discoidal HDL (rHDL), we show a glucose uptake effect comparable to insulin. Increased plasma membrane GLUT4 levels in ex vivo rHDL-stimulated myofibers from HA-GLUT4-GFP transgenic mice support this observation. rHDL increased phosphorylation of AMP kinase (AMPK) and acetyl-coA carboxylase (ACC) but not Akt. A survey of domain-specific peptides of apoA-I showed that the lipid-free C-terminal 190-243 fragment increases plasma membrane GLUT4, promotes glucose uptake, and activates AMPK signaling but not Akt. This may be explained by changes in alpha-helical content of 190-243 fragment versus full-length lipid-free apoA-I as assessed by circular dichroism spectroscopy. Discoidal HDL and the 190-243 peptide of apoA-I are potent agonists of glucose uptake in skeletal muscle, and the C-terminal alpha-helical content of apoA-I may be an important determinant of this effect.-Dalla-Riva, J., K. G. Stenkula, J. Petrlova, and J. O. Lagerstedt. Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle. J. Lipid Res. 2013. 54: 1275-1282.
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