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Retinoic acid receptor β2 agonists restore glycaemic control in diabetes and reduce steatosis.

Published on Feb 1, 2016in Diabetes, Obesity and Metabolism6.13
· DOI :10.1111/dom.12590
Steven E. Trasino5
Estimated H-index: 5
(Cornell University),
Xiao-Han Tang11
Estimated H-index: 11
(Cornell University)
+ 1 AuthorsLorraine J. Gudas48
Estimated H-index: 48
(Cornell University)
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Abstract
To investigate the effects of specific retinoic acid receptor (RAR) agonists in diabetes and fatty liver disease.Synthetic agonists for RARβ2 were administered to wild-type (wt) mice in a model of high-fat-diet (HFD)-induced type 2 diabetes (T2D) and to ob/ob and db/db mice (genetic models of obesity-associated T2D).We show that administration of synthetic agonists for RARβ2 to either wt mice in a model of HFD-induced T2D or to ob/ob and db/db mice reduces hyperglycaemia, peripheral insulin resistance and body weight. Furthermore, RARβ2 agonists dramatically reduce steatosis, lipid peroxidation and oxidative stress in the liver, pancreas and kidneys of obese, diabetic mice. RARβ2 agonists also lower levels of mRNAs involved in lipogenesis, such as sterol regulatory element-binding transcription factor 1 (SREBP1) and fatty acid synthase, and increase mRNAs that mediate mitochondrial fatty acid β-oxidation, such as CPT1α, in these organs. RARβ2 agonists lower triglyceride levels in these organs, and in muscle.Collectively, our data show that orally active, rapid-acting, high-affinity pharmacological agonists for RARβ2 improve the diabetic phenotype while reducing lipid levels in key insulin target tissues. We suggest that RARβ2 agonists should be useful drugs for T2D therapy and for treatment of hepatic steatosis.
  • References (46)
  • Citations (13)
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References46
Newest
#1Steven E. Trasino (Cornell University)H-Index: 5
#2Yannick D. Benoit (Cornell University)H-Index: 14
Last.Lorraine J. Gudas (Cornell University)H-Index: 48
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#1Yu Ah Hong (KU: Korea University)H-Index: 5
#2Ji Hee Lim (Catholic University of Korea)H-Index: 14
Last.Hyung Wook Kim (Catholic University of Korea)H-Index: 14
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#1Seong Chul Kim (NEOMED: Northeast Ohio Medical University)H-Index: 2
#2Chunki Kim (NEOMED: Northeast Ohio Medical University)H-Index: 4
Last.David J. Moore Mbbs (BCM: Baylor College of Medicine)H-Index: 69
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#1Pierre-Jacques Brun (Columbia University)H-Index: 5
#2Kryscilla Jian Zhang Yang (Columbia University)H-Index: 4
Last.William S. Blaner (Columbia University)H-Index: 60
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#1Hiroyuki Tsuchiya (Kyoto Pharmaceutical University)H-Index: 43
#2Yoshito Ikeda (Kyoto Pharmaceutical University)H-Index: 4
Last.Shoko Oshiro (Kyoto Pharmaceutical University)H-Index: 1
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Cited By13
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#1Chao-Hung Chen (KMU: Kaohsiung Medical University)H-Index: 2
#2Kun-Der Lin (KMU: Kaohsiung Medical University)H-Index: 13
Last.Pi-Jung Hsiao (KMU: Kaohsiung Medical University)H-Index: 2
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#1J. Esteban (Universidad Miguel Hernández de Elche)H-Index: 3
#2Marina Serrano-Maciá (Universidad Miguel Hernández de Elche)
Last.J. Barril (Universidad Miguel Hernández de Elche)H-Index: 4
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#1Steven E. Trasino (CUNY: City University of New York)H-Index: 1
#2Xiao-Han Tang (CUNY: City University of New York)H-Index: 1
Last.Lorraine J. Gudas (CUNY: City University of New York)H-Index: 1
view all 5 authors...
#1Lana M. Pollock (Cleveland Clinic)H-Index: 1
#2Jing Xie (Cleveland Clinic)H-Index: 3
Last.Bela Anand-Apte (Cleveland Clinic Lerner College of Medicine)H-Index: 30
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#1Di Yang (University of California, Berkeley)H-Index: 2
#2Marta G. Vuckovic (University of California, Berkeley)H-Index: 1
Last.Joseph L. Napoli (University of California, Berkeley)H-Index: 33
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