The Role of the Niemann-Pick Disease, Type C1 Protein in Adipocyte Insulin Action

被引：19

作者：

Fletcher, Rachael ^{[1
]}

Gribben, Christopher ^{[1
]}

Ma, Xuiquan ^{[1
]}

Burchfield, James G. ^{[1
]}

Thomas, Kristen C. ^{[1
]}

Krycer, James R. ^{[1
,2
]}

James, David E. ^{[1
,3
]}

Fazakerley, Daniel J. ^{[1
]}

机构：

[1] Garvan Inst Med Res, Diabet & Obes Program, Sydney, NSW, Australia

[2] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia

[3] Univ Sydney, Sch Mol Biosci, Charles Perkins Ctr, Sydney, NSW 2006, Australia

来源：

PLOS ONE | 2014年 / 9卷 / 04期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GLUCOSE TRANSPORTERS; SUSCEPTIBILITY LOCI; CHOLESTEROL TRAFFICKING; GLUT4; GENE; RECEPTOR; LOCALIZATION; METABOLISM; ACTIVATION; EXPRESSION;

D O I：

10.1371/journal.pone.0095598

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Niemann-Pick disease, type C1 (NPC1) gene encodes a transmembrane protein involved in cholesterol efflux from the lysosome. SNPs within NPC1 have been associated with obesity and type 2 diabetes, and mice heterozygous or null for NPC1 are insulin resistant. However, the molecular mechanism underpinning this association is currently undefined. This study aimed to investigate the effects of inhibiting NPC1 function on insulin action in adipocytes. Both pharmacological and genetic inhibition of NPC1 impaired insulin action. This impairment was evident at the level of insulin signalling and insulin-mediated glucose transport in the short term and decreased GLUT4 expression due to reduced liver X receptor (LXR) transcriptional activity in the long-term. These data show that cholesterol homeostasis through NPC1 plays a crucial role in maintaining insulin action at multiple levels in adipocytes.

引用

页数：10

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