The LRC-TriCEPS platform identified 2 new receptors for ApoA-1, potentially new drug targets for Diabetes Type 2
November 15, 2024
Intro
Apolipoprotein A-I priming via SR-BI and ABCA1 receptor binding upregulates mitochondrial metabolism to promote insulin secretion in INS-1E cells
Abstract
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. 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 type 2 diabetes therapies. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0311039Author
Social Media
