Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease

被引：199

作者：

Dong, Bingning ^{[2
]}

Saha, Pradip K. ^{[3
]}

Huang, Wendong ^{[4
]}

Chen, Wenling ^{[5
]}

Abu-Elheiga, Lutfi A. ^{[1
]}

Wakil, Salih J. ^{[1
]}

Stevens, Robert D. ^{[6
]}

Ilkayeva, Olga ^{[6
]}

Newgard, Christopher B. ^{[6
]}

Chan, Lawrence ^{[3
]}

Moore, David D. ^{[2
,3
]}

机构：

[1] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[3] Baylor Coll Med, Div Endocrinol Diabet & Metab, Dept Med, Houston, TX 77030 USA

[4] City Hope Natl Med Ctr, Beckman Res Inst, Dept Gene Regulat & Drug Discovery, Duarte, CA 91010 USA

[5] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA

[6] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 44期

基金：

美国国家卫生研究院;

关键词：

insulin resistance; nuclear receptor; xenobiotics; CONSTITUTIVE ANDROSTANE RECEPTOR; INSULIN-RESISTANCE; DRUG-METABOLISM; X-RECEPTOR; CROSS-TALK; LIPID HOMEOSTASIS; ENZYME INDUCERS; ACID OXIDATION; MALONYL-COA; MICE;

D O I：

10.1073/pnas.0909731106

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：

Constitutive androstane receptor CAR (NR1I3) has been identified as a central mediator of coordinate responses to xenobiotic and endobiotic stress. Here we use leptin-deficient mice (ob/ob) and ob/ob, CAR(-/-) double mutant mice to identify a metabolic role of CAR in type 2 diabetes. Activation of CAR significantly reduces serum glucose levels and improves glucose tolerance and insulin sensitivity. Gene expression analyses and hyperinsulinemic euglycemic clamp results suggest that CAR activation ameliorates hyperglycemia by suppressing glucose production and stimulating glucose uptake and usage in the liver. In addition, CAR activation dramatically improves fatty liver by both inhibition of hepatic lipogenesis and induction of beta-oxidation. We conclude that CAR activation improves type 2 diabetes, and that these actions of CAR suggest therapeutic approaches to the disease.

引用

页码：18831 / 18836

页数：6

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