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Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease.

Publication ,  Journal Article
Dong, B; Saha, PK; Huang, W; Chen, W; Abu-Elheiga, LA; Wakil, SJ; Stevens, RD; Ilkayeva, O; Newgard, CB; Chan, L; Moore, DD
Published in: Proc Natl Acad Sci U S A
November 3, 2009

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.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 3, 2009

Volume

106

Issue

44

Start / End Page

18831 / 18836

Location

United States

Related Subject Headings

  • Sulfotransferases
  • Receptors, Cytoplasmic and Nuclear
  • Oxidation-Reduction
  • Mice, Obese
  • Mice
  • Liver
  • Lipogenesis
  • Insulin
  • Glucose Tolerance Test
  • Gene Expression Regulation
 

Citation

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Dong, B., Saha, P. K., Huang, W., Chen, W., Abu-Elheiga, L. A., Wakil, S. J., … Moore, D. D. (2009). Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A, 106(44), 18831–18836. https://doi.org/10.1073/pnas.0909731106
Dong, Bingning, Pradip K. Saha, Wendong Huang, Wenling Chen, Lutfi A. Abu-Elheiga, Salih J. Wakil, Robert D. Stevens, et al. “Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease.Proc Natl Acad Sci U S A 106, no. 44 (November 3, 2009): 18831–36. https://doi.org/10.1073/pnas.0909731106.
Dong B, Saha PK, Huang W, Chen W, Abu-Elheiga LA, Wakil SJ, et al. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18831–6.
Dong, Bingning, et al. “Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease.Proc Natl Acad Sci U S A, vol. 106, no. 44, Nov. 2009, pp. 18831–36. Pubmed, doi:10.1073/pnas.0909731106.
Dong B, Saha PK, Huang W, Chen W, Abu-Elheiga LA, Wakil SJ, Stevens RD, Ilkayeva O, Newgard CB, Chan L, Moore DD. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18831–18836.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 3, 2009

Volume

106

Issue

44

Start / End Page

18831 / 18836

Location

United States

Related Subject Headings

  • Sulfotransferases
  • Receptors, Cytoplasmic and Nuclear
  • Oxidation-Reduction
  • Mice, Obese
  • Mice
  • Liver
  • Lipogenesis
  • Insulin
  • Glucose Tolerance Test
  • Gene Expression Regulation