DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism.
DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism.
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DOI：
10.1007/s00380-020-01711-z
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发表时间：
2021-01
影响因子：
1.5
通讯作者：
Kurabayashi M
中科院分区：
文献类型：
--
作者：
Furukawa N;Koitabashi N;Matsui H;Sunaga H;Umbarawan Y;Syamsunarno MRAA;Yamaguchi A;Obokata M;Hanaoka H;Yokoyama T;Kurabayashi M
二肽基肽酶-4（DPP-4）抑制剂是广泛用于治疗2型糖尿病的基于肠促胰岛素的疗法。我们研究了DPP-4抑制剂vildagelatin（vilda）对压力超负荷下心肌代谢和心脏功能的心脏保护作用。用载体或vilda处理小鼠，然后进行横向主动脉缩窄（TAC）。TAC治疗3周后，vilda治疗组小鼠的心脏肥大和收缩功能损害减轻。压力-容积分析显示，Vilda治疗显著改善TAC心脏的左室收缩效率。心肌能量底物分析表明，vilda治疗显着增加葡萄糖摄取以及脂肪酸摄取。成纤维细胞生长因子21（FGF 21），一种参与能量代谢调节的肽，在TAC心脏中增加，并通过vilda处理进一步增加。在TAC和Vilda处理后，小鼠心脏成纤维细胞中的FGF 21强于心肌细胞中的FGF 21表达。Vilda处理通过sirtuin（Sirt）1介导的途径显著诱导人心脏成纤维细胞中的FGF 21表达，表明成纤维细胞介导的FGF 21表达可以调节能量代谢并在应激心脏中发挥Vilda介导的有益作用。Vilda通过Sirt 1诱导心脏成纤维细胞中的代谢调节因子FGF 21表达，并增加小鼠压力超负荷心脏的收缩效率。
Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (vilda), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or vilda, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in vilda-treated mice. Pressure–volume analysis showed that vilda treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that vilda treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by vilda treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with vilda treatment. Vilda treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert vilda-mediated beneficial effects in stressed heart. Vilda induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.6
作者：
Chou RH;Huang PH;Hsu CY;Chang CC;Leu HB;Huang CC;Chen JW;Lin SJ
通讯作者：
Lin SJ
影响因子：
13
作者：
McMurray, John J. V.;Ponikowski, Piotr;Krum, Henry
通讯作者：
Krum, Henry
影响因子：
120.7
作者：
Levy, D;Larson, MG;Ho, KKL
通讯作者：
Ho, KKL
循环的FGF21是肝脏的，并在进食和过度喂养过程中增强了葡萄糖的摄取。
影响因子：
7.7
作者：
Markan KR;Naber MC;Ameka MK;Anderegg MD;Mangelsdorf DJ;Kliewer SA;Mohammadi M;Potthoff MJ
通讯作者：
Potthoff MJ