Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.
Författare
Summary, in English
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 if nascent discoidal HDL, in which apoA-I attains a different conformation from mature HDL and lipid-free states, could induce muscle glucose uptake and if 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 α-helical content of 190-243 fragment versus full-length lipid-free apoA-I as assessed by circular dichroism spectroscopy. JLR Discoidal HDL and the 190-243 peptide of apoA-I are potent agonists of glucose uptake in skeletal muscle and the C-terminal α-helical content of apoA-I may be an important determinant of this effect.
Avdelning/ar
- Medical Protein Science
- EXODIAB: Excellence of Diabetes Research in Sweden
Publiceringsår
2013
Språk
Engelska
Sidor
1275-1282
Publikation/Tidskrift/Serie
Journal of Lipid Research
Volym
54
Issue
5
Fulltext
- Available as PDF - 1016 kB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Biochemistry and Molecular Biology
Ämne
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Medical Protein Science
ISBN/ISSN/Övrigt
- ISSN: 1539-7262