Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.
(2013) In Journal of Lipid Research 54(5). p.1275-1282- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3628434
- author
- Dalla-Riva, Jonathan LU ; Stenkula, Karin LU ; Petrlova, Jitka LU and Lagerstedt, Jens LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Lipid Research
- volume
- 54
- issue
- 5
- pages
- 1275 - 1282
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000317394300014
- pmid:23471027
- scopus:84876802423
- pmid:23471027
- ISSN
- 1539-7262
- DOI
- 10.1194/jlr.M032904
- language
- English
- LU publication?
- yes
- id
- bce674af-efbc-4550-b6eb-c71c1b838d45 (old id 3628434)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23471027?dopt=Abstract
- date added to LUP
- 2016-04-01 10:41:32
- date last changed
- 2022-04-04 20:27:50
@article{bce674af-efbc-4550-b6eb-c71c1b838d45, abstract = {{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.}}, author = {{Dalla-Riva, Jonathan and Stenkula, Karin and Petrlova, Jitka and Lagerstedt, Jens}}, issn = {{1539-7262}}, language = {{eng}}, number = {{5}}, pages = {{1275--1282}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Lipid Research}}, title = {{Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.}}, url = {{https://lup.lub.lu.se/search/files/2057591/3865460.pdf}}, doi = {{10.1194/jlr.M032904}}, volume = {{54}}, year = {{2013}}, }