PMID- 30970222
OWN - NLM
STAT- MEDLINE
DCOM- 20200520
LR  - 20200520
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 7
DP  - 2019 Jul
TI  - Apolipoprotein A-I improves pancreatic beta-cell function independent of the 
      ATP-binding cassette transporters ABCA1 and ABCG1.
PG  - 8479-8489
LID - 10.1096/fj.201802512RR [doi]
AB  - 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 G(1) (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.
FAU - Hou, Liming
AU  - Hou L
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Tang, Shudi
AU  - Tang S
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Wu, Ben J
AU  - Wu BJ
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Ong, Kwok-Leung
AU  - Ong KL
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Westerterp, Marit
AU  - Westerterp M
AD  - Section Molecular Genetics, Department of Pediatrics, University of 
      Groningen-University Medical Center Groningen, Groningen, The Netherlands.
FAU - Barter, Philip J
AU  - Barter PJ
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Cochran, Blake J
AU  - Cochran BJ
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Tabet, Fatiha
AU  - Tabet F
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
FAU - Rye, Kerry-Anne
AU  - Rye KA
AD  - Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University 
      of New South Wales Sydney, Sydney, New South Wales, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190410
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ABCG1 protein, human)
RN  - 0 (APOA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Insulin)
RN  - 0 (Lipoproteins)
RN  - 0 (Lipoproteins, HDL)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/*metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/*metabolism
MH  - Animals
MH  - Apolipoprotein A-I/*metabolism
MH  - Biological Transport/physiology
MH  - Cholesterol/metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Insulin/metabolism
MH  - Insulin-Secreting Cells/*metabolism
MH  - Lipid Metabolism/physiology
MH  - Lipoproteins/metabolism
MH  - Lipoproteins, HDL/metabolism
MH  - Male
MH  - Mice
OTO - NOTNLM
OT  - apoA-I
OT  - cholesterol metabolism
OT  - glucose metabolism
OT  - inflammation
OT  - beta cells
EDAT- 2019/04/11 06:00
MHDA- 2020/05/21 06:00
CRDT- 2019/04/11 06:00
PHST- 2019/04/11 06:00 [pubmed]
PHST- 2020/05/21 06:00 [medline]
PHST- 2019/04/11 06:00 [entrez]
AID - 10.1096/fj.201802512RR [doi]
PST - ppublish
SO  - FASEB J. 2019 Jul;33(7):8479-8489. doi: 10.1096/fj.201802512RR. Epub 2019 Apr 10.