| First Author | Hou L | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 7 | Pages | 8479-8489 |
| PubMed ID | 30970222 | Mgi Jnum | J:292645 |
| Mgi Id | MGI:6448771 | Doi | 10.1096/fj.201802512RR |
| Citation | Hou L, et al. (2019) Apolipoprotein A-I improves pancreatic beta-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1. FASEB J 33(7):8479-8489 |
| abstractText | Apolipoprotein A-I (apoA-I), the main protein constituent of HDLs, increases insulin synthesis and insulin secretion in pancreatic beta cells. ApoA-I also accepts cholesterol that effluxes from cells expressing ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1). Mice with conditional deletion of ABCA1 and ABCG1 in beta cells [beta-double knockout (DKO) mice] have increased islet cholesterol levels and reduced glucose-stimulated insulin secretion (GSIS). The project asks whether metabolic pathways are dysregulated in beta-DKO mouse islets and whether this can be corrected, and GSIS improved, by treatment with apoA-I. beta-DKO mice were treated with apoA-I or PBS, and islets were isolated for determination of GSIS. Total RNA was extracted from beta-DKO and control mouse islets for microarray analysis. Metabolic pathways were interrogated by functional enrichment analysis. ApoA-I treatment improved GSIS in beta-DKO but not control mouse islets. Plasma lipid and lipoprotein levels and islet cholesterol levels were also unaffected by treatment with apoA-I. Cholesterol metabolism, glucose metabolism, and inflammation pathways were dysregulated in beta-DKO mouse islets. This was not corrected by treatment with apoA-I. In summary, apoA-I treatment improves GSIS by a cholesterol-independent mechanism, but it does not correct metabolic dysregulation in beta-DKO mouse islets.-Hou, L., Tang, S., Wu, B. J., Ong, K.-L., Westerterp, M., Barter, P. J., Cochran, B. J., Tabet, F., Rye, K.-A. Apolipoprotein A-I improves pancreatic beta-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1. |
