Apolipoprotein A-I improves pancreatic ß-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1.
FASEB J
; 33(7): 8479-8489, 2019 07.
Article
in En
| MEDLINE
| ID: mdl-30970222
ABSTRACT
Apolipoprotein A-I (apoA-I), the main protein constituent of HDLs, increases insulin synthesis and insulin secretion in pancreatic ß 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 ß cells [ß-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 ß-DKO mouse islets and whether this can be corrected, and GSIS improved, by treatment with apoA-I. ß-DKO mice were treated with apoA-I or PBS, and islets were isolated for determination of GSIS. Total RNA was extracted from ß-DKO and control mouse islets for microarray analysis. Metabolic pathways were interrogated by functional enrichment analysis. ApoA-I treatment improved GSIS in ß-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 ß-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 ß-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 ß-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoprotein A-I
/
Insulin-Secreting Cells
/
ATP Binding Cassette Transporter 1
/
ATP Binding Cassette Transporter, Subfamily G, Member 1
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Australia