Apolipoprotein A-I priming via SR-BI and ABCA1 receptor binding upregulates mitochondrial metabolism to promote insulin secretion in INS-1E cells
Lyons, Claire L. LU ; Cowan, Elaine LU
; Nilsson, Oktawia
LU
; Mohar, Manca
; Peña-Martínez, Pablo
LU
; Eliasson, Lena
LU
and Lagerstedt, Jens O.
LU
(2024)
In PLoS ONE
19(11 November).
- Abstract
Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors. Identified targets, alongside ATP binding cassette transporter A1 (ABCA1) (included control) were silenced in the same cells, and insulin secretion (ELISA) and mitochondrial metabolism (seahorse) were assessed with/without ApoA-I priming. Human β-cell expression data was used to investigate... (More)
Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors. Identified targets, alongside ATP binding cassette transporter A1 (ABCA1) (included control) were silenced in the same cells, and insulin secretion (ELISA) and mitochondrial metabolism (seahorse) were assessed with/without ApoA-I priming. Human β-cell expression data was used to investigate ApoA-I receptor pathways in type 2 diabetes (T2D). Scavenger receptor B1 (SR-BI) and regulator of microtubule dynamics 1 were identified as ApoA-I targets. SR-BI or ABCA1 silencing abolished ApoA-I induced increases in insulin secretion. ApoA-I priming increased mitochondrial OXPHOS, however this was greatly attenuated with SR-BI or ABCA1 silencing. Supporting this, human β-cell expression data investigations found SR-BI and ABCA1 to be correlated with genes associated with mitochondrial pathways. In all, SR-BI and ABCA1 correlated with 73 and 3 genes differentially expressed in T2D, respectively. We confirm that SR-BI and ABCA1 are the primary β-cell ApoA-I receptors and demonstrate that ApoA-I priming enhances β-cell insulin secretion via the upregulation of mitochondrial metabolism through ApoA-I-SR-BI and ApoA-I-ABCA1 pathways. We propose that SR-BI relies on mitochondrial and exocytotic pathways, while ABCA1 depends solely on mitochondrial pathways. Our findings uncover new targets in ApoA-I β-cell mechanism for T2D therapies.
(Less)
- author
- Lyons, Claire L.
LU
; Cowan, Elaine
LU
; Nilsson, Oktawia
LU
; Mohar, Manca
; Peña-Martínez, Pablo
LU
; Eliasson, Lena
LU
and Lagerstedt, Jens O.
LU
- organization
- publishing date
- 2024-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 19
- issue
- 11 November
- article number
- e0311039
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- scopus:85209371967
- pmid:39546458
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0311039
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: Copyright: © 2024 Lyons et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- id
- 52860db8-6e34-4149-9c8c-78f2cccebf25
- date added to LUP
- 2025-01-14 15:28:28
- date last changed
- 2025-01-28 16:57:07
@article{52860db8-6e34-4149-9c8c-78f2cccebf25,
abstract = {{<p>Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors. Identified targets, alongside ATP binding cassette transporter A1 (ABCA1) (included control) were silenced in the same cells, and insulin secretion (ELISA) and mitochondrial metabolism (seahorse) were assessed with/without ApoA-I priming. Human β-cell expression data was used to investigate ApoA-I receptor pathways in type 2 diabetes (T2D). Scavenger receptor B1 (SR-BI) and regulator of microtubule dynamics 1 were identified as ApoA-I targets. SR-BI or ABCA1 silencing abolished ApoA-I induced increases in insulin secretion. ApoA-I priming increased mitochondrial OXPHOS, however this was greatly attenuated with SR-BI or ABCA1 silencing. Supporting this, human β-cell expression data investigations found SR-BI and ABCA1 to be correlated with genes associated with mitochondrial pathways. In all, SR-BI and ABCA1 correlated with 73 and 3 genes differentially expressed in T2D, respectively. We confirm that SR-BI and ABCA1 are the primary β-cell ApoA-I receptors and demonstrate that ApoA-I priming enhances β-cell insulin secretion via the upregulation of mitochondrial metabolism through ApoA-I-SR-BI and ApoA-I-ABCA1 pathways. We propose that SR-BI relies on mitochondrial and exocytotic pathways, while ABCA1 depends solely on mitochondrial pathways. Our findings uncover new targets in ApoA-I β-cell mechanism for T2D therapies.</p>}},
author = {{Lyons, Claire L. and Cowan, Elaine and Nilsson, Oktawia and Mohar, Manca and Peña-Martínez, Pablo and Eliasson, Lena and Lagerstedt, Jens O.}},
issn = {{1932-6203}},
language = {{eng}},
number = {{11 November}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Apolipoprotein A-I priming via SR-BI and ABCA1 receptor binding upregulates mitochondrial metabolism to promote insulin secretion in INS-1E cells}},
url = {{http://dx.doi.org/10.1371/journal.pone.0311039}},
doi = {{10.1371/journal.pone.0311039}},
volume = {{19}},
year = {{2024}},
}