PMID- 30278109
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 2
DP  - 2019 Feb
TI  - Insulin increases cholesterol uptake, lipid droplet content, and apolipoprotein B 
      secretion in CaCo-2 cells by upregulating SR-BI via a PI3K, AKT, and 
      mTOR-dependent pathway.
PG  - 1550-1559
LID - 10.1002/jcb.27410 [doi]
AB  - The actions of insulin on intestinal cholesterol absorption and lipoprotein 
      secretion are not well understood. Herein, we determined the effects of insulin 
      on the levels of cholesterol transporter scavenger receptor, class B, type I 
      (SR-BI), cellular cholesterol uptake, intracellular lipid accumulation, and 
      lipoprotein secretion in a cellular model of human intestinal epithelium. 
      METHODS: CaCo-2 cells were cultured to postconfluency in Transwell filters and 
      stimulated with glucose (25 mM) in the presence or absence of insulin (100 nM) at 
      their basolateral surface. SR-BI mRNA and protein levels were quantified by 
      quantitative reverse transcription-PCR and immunoblot, respectively. Polarized 
      localization of SR-BI was determined by cell surface proteins biotinylation and 
      streptavidin precipitation. Activities of PI3K, AKT, mTOR, and SR-BI were 
      pharmacologically antagonized. Cholesterol uptake was assessed by NBD-cholesterol 
      incorporation. Apolipoprotein (apo) B concentration was quantified by ELISA. 
      Subcellular localization of neutral lipids (BODIPY) and SR-BI 
      (immunofluorescence) was determined by confocal microscopy. RESULTS: In polarized 
      CaCo-2 cells, insulin increased SR-BI at the mRNA and protein levels. SR-BI was 
      exclusively present at apical cell surface, as indicated by biotinylation and 
      confocal microscopy analysis. Glucose did not modify SR-BI abundance or 
      subcellular localization. Effects of insulin on SR-BI levels were abrogated by 
      PI3K, AKT, or mTOR pharmacological antagonism. Cholesterol uptake, neutral lipid 
      abundance, and apo B secretion were increased by insulin in CaCo-2 cells, and 
      these effects were prevented by SR-BI pharmacological antagonism with block lipid 
      transport-1. CONCLUSIONS: insulin promotes cholesterol uptake, intracellular 
      lipid store, and apo B-containing lipoproteins secretion by SR-BI-dependent 
      mechanisms in a model of human intestinal epithelium.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Fuentes, Marcela
AU  - Fuentes M
AD  - Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Santander, Nicolas
AU  - Santander N
AD  - Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
FAU - Cortes, Victor
AU  - Cortes V
AUID- ORCID: 0000-0002-1658-0965
AD  - Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia 
      Universidad Catolica de Chile, Santiago, Chile.
LA  - eng
GR  - 21130444/Comision Nacional de Investigacion Cientifica y Tecnologica/
GR  - 1181214/Fondo Nacional de Desarrollo Cientifico y Tecnologico/
GR  - 3150661/Fondo Nacional de Desarrollo Cientifico y Tecnologico/
PT  - Journal Article
DEP - 20181002
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
SB  - IM
OTO - NOTNLM
OT  - CaCo-2 cells
OT  - cholesterol
OT  - insulin
OT  - intestine
OT  - lipoprotein
OT  - scavenger receptor, class B, type I (SR-BI)
EDAT- 2018/10/03 06:00
MHDA- 2018/10/03 06:01
CRDT- 2018/10/03 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/07/10 00:00 [accepted]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2018/10/03 06:01 [medline]
PHST- 2018/10/03 06:00 [entrez]
AID - 10.1002/jcb.27410 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Feb;120(2):1550-1559. doi: 10.1002/jcb.27410. Epub 2018 Oct 
      2.