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Jens Lagerstedt

Associate professor

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Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.

Author

  • Jonathan Dalla-Riva
  • Karin Stenkula
  • Jitka Petrlova
  • Jens Lagerstedt

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.

Department/s

  • Medical Protein Science
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2013

Language

English

Pages

1275-1282

Publication/Series

Journal of Lipid Research

Volume

54

Issue

5

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 1539-7262