A short peptide of the C-terminal class Y helices of apolipoprotein A-I has preserved functions in cholesterol efflux and in vivo metabolic control
(2020) In Scientific Reports 10(1).- Abstract
Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) induces glucose uptake by muscle tissues and stimulates pancreatic insulin secretion, and also facilitates cholesterol transport in circulation, and is explored for anti-diabetic and anti-atherosclerotic treatments. As the better alternative to complex protein–lipid formulations it was recently established that the C-terminal region of the ApoA-I protein singly improves the metabolic control and prevents formation of atherosclerotic plaques. Additional investigations of peptides based on the ApoA-I structure may lead to novel anti-diabetic drugs. We here investigate a short peptide (33mer, RG33) that corresponds to the two last helical segments (aa 209–241) of the ApoA-I... (More)
Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) induces glucose uptake by muscle tissues and stimulates pancreatic insulin secretion, and also facilitates cholesterol transport in circulation, and is explored for anti-diabetic and anti-atherosclerotic treatments. As the better alternative to complex protein–lipid formulations it was recently established that the C-terminal region of the ApoA-I protein singly improves the metabolic control and prevents formation of atherosclerotic plaques. Additional investigations of peptides based on the ApoA-I structure may lead to novel anti-diabetic drugs. We here investigate a short peptide (33mer, RG33) that corresponds to the two last helical segments (aa 209–241) of the ApoA-I structure (so-called class Y-helices which forms amphipathic helices) for stability and solubility in serum, for in vitro cholesterol efflux capability, and for providing in vivo glucose control in an insulin resistant mouse model. The RG33 peptide efficiently solubilizes lipid-vesicles, and promotes the efflux of cholesterol from cultured macrophages. The efflux capacity is significantly increased in the presence of lipids compared to non-lipidated RG33. Finally, acute treatment with the RG33 peptide significantly improves the glucose clearance capacity of insulin resistant mice. The impact of the RG33 peptide on glucose control and cholesterol transport, as well as the physicochemical properties, makes it a good candidate for translational exploration of its therapeutic potential in diabetes treatment.
(Less)
- author
- Edmunds, Shelley J. LU ; Liébana-García, Rebeca ; Stenkula, Karin G. LU and Lagerstedt, Jens O. LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 10
- issue
- 1
- article number
- 18070
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:33093642
- scopus:85093860981
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-020-75232-0
- language
- English
- LU publication?
- yes
- id
- 24b2e4cf-0744-47ab-847b-f236817e63de
- date added to LUP
- 2020-11-04 13:29:30
- date last changed
- 2024-10-03 11:33:00
@article{24b2e4cf-0744-47ab-847b-f236817e63de,
abstract = {{<p>Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) induces glucose uptake by muscle tissues and stimulates pancreatic insulin secretion, and also facilitates cholesterol transport in circulation, and is explored for anti-diabetic and anti-atherosclerotic treatments. As the better alternative to complex protein–lipid formulations it was recently established that the C-terminal region of the ApoA-I protein singly improves the metabolic control and prevents formation of atherosclerotic plaques. Additional investigations of peptides based on the ApoA-I structure may lead to novel anti-diabetic drugs. We here investigate a short peptide (33mer, RG33) that corresponds to the two last helical segments (aa 209–241) of the ApoA-I structure (so-called class Y-helices which forms amphipathic helices) for stability and solubility in serum, for in vitro cholesterol efflux capability, and for providing in vivo glucose control in an insulin resistant mouse model. The RG33 peptide efficiently solubilizes lipid-vesicles, and promotes the efflux of cholesterol from cultured macrophages. The efflux capacity is significantly increased in the presence of lipids compared to non-lipidated RG33. Finally, acute treatment with the RG33 peptide significantly improves the glucose clearance capacity of insulin resistant mice. The impact of the RG33 peptide on glucose control and cholesterol transport, as well as the physicochemical properties, makes it a good candidate for translational exploration of its therapeutic potential in diabetes treatment.</p>}},
author = {{Edmunds, Shelley J. and Liébana-García, Rebeca and Stenkula, Karin G. and Lagerstedt, Jens O.}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{A short peptide of the C-terminal class Y helices of apolipoprotein A-I has preserved functions in cholesterol efflux and in vivo metabolic control}},
url = {{http://dx.doi.org/10.1038/s41598-020-75232-0}},
doi = {{10.1038/s41598-020-75232-0}},
volume = {{10}},
year = {{2020}},
}