Activation of retinoid receptor-mediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats.
Activation of retinoid receptor-mediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats.
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DOI：
10.1016/j.yjmcc.2013.01.017
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发表时间：
2013-04
影响因子：
5
通讯作者：
Pan, Jing
中科院分区：
文献类型：
--
作者：
Guleria, Rakeshwar S.;Singh, Amar B.;Nizamutdinova, Irina T.;Souslova, Tatiana;Mohammad, Amin A.;Kendall, Jonathan A., Jr.;Baker, Kenneth M.;Pan, Jing
关键词：
糖尿病心肌病（DCM）是糖尿病和代谢综合征相关发病率和死亡率的一个重要因素。类维生素A通过激活视黄酸受体（RAR）和类维生素A×受体（RXR），与控制葡萄糖和脂质稳态有关，对肥胖和糖尿病有影响。然而，RAR 和 RXR 在 DCM 发展中的功能作用仍不清楚。 Zucker 糖尿病肥胖 (ZDF) 和瘦大鼠接受 Am580（RARα 激动剂）或 LGD1069（RXR 激动剂）治疗 16 周，并测定心脏功能和代谢变化。 ZDF大鼠出现高血糖、高脂血症和胰岛素抵抗。 ZDF 大鼠糖尿病心肌病的特点是氧化应激、细胞凋亡、纤维化、炎症增加、MAP 激酶和 NF-κB 信号传导激活以及 Akt 磷酸化减弱，同时葡萄糖转运减少和心脏脂质积累增加，最终导致舒张功能障碍。 Am580 和 LGD1069 通过改善葡萄糖耐量和胰岛素抵抗，减轻糖尿病引起的心功能障碍和病理改变；促进 Akt 激活和葡萄糖利用，并减轻氧化应激和相关的 MAP 激酶和 NF-κB 信号通路。 Am580 抑制 ZDF 大鼠体重增加，减弱心脏脂肪酸摄取、β-氧化和脂质积累的增加。然而，LGD1069促进体重增加、高脂血症和心脏脂质积累。总之，我们的数据表明 RAR 和 RXR 的激活可能在糖尿病心肌病的治疗中具有治疗潜力。然而，还需要进一步的研究来阐明 RAR 和 RXR 在脂质代谢和稳态调节中的作用。
Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. Retinoids, through activation of retinoic acid receptor (RAR) and retinoid×receptor (RXR), have been linked to control of glucose and lipid homeostasis, with effects on obesity and diabetes. However, the functional role of RAR and RXR in the development of DCM remains unclear. Zucker diabetic fatty (ZDF) and lean rats were treated with Am580 (RARα agonist) or LGD1069 (RXR agonist) for 16 weeks, and cardiac function and metabolic alterations were determined. Hyperglycemia, hyperlipidemia and insulin resistance were observed in ZDF rats. Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction. Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways. Am580 inhibited body weight gain, attenuated the increased cardiac fatty acid uptake, β-oxidation and lipid accumulation in the hearts of ZDF rats. However, LGD1069 promoted body weight gain, hyperlipidemia and cardiac lipid accumulation. In conclusion, our data suggest that activation of RAR and RXR may have therapeutic potential in the treatment of diabetic cardiomyopathy. However, further studies are necessary to clarify the role of RAR and RXR in the regulation of lipid metabolism and homeostasis.
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影响因子：
5
作者：
Bugger H;Riehle C;Jaishy B;Wende AR;Tuinei J;Chen D;Soto J;Pires KM;Boudina S;Theobald HA;Luptak I;Wayment B;Wang X;Litwin SE;Weimer BC;Abel ED
通讯作者：
Abel ED
影响因子：
1.7
作者：
Maisch, B.;Alter, P.;Pankuweit, S.
通讯作者：
Pankuweit, S.
影响因子：
18.2
作者：
Daniels, Anneleen;Linz, Dominik;van Nieuwenhoven, Frans A.
通讯作者：
van Nieuwenhoven, Frans A.
影响因子：
10.8
作者：
Mariappan, Nithya;Elks, Carrie M.;Francis, Joseph
通讯作者：
Francis, Joseph
DOI：
10.1152/ajpheart.01301.2007
发表时间：
2008-02-01
影响因子：
4.8
作者：
Choudhary, Rashmi;Palm-Leis, Ants;Pan, Jing
通讯作者：
Pan, Jing