Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy.
Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy.
复制标题
DOI：
10.1016/j.yjmcc.2009.08.028
复制
发表时间：
2009-11
影响因子：
5
通讯作者：
Komuro I
中科院分区：
文献类型：
--
作者：
Ikeda H;Shiojima I;Ozasa Y;Yoshida M;Holzenberger M;Kahn CR;Walsh K;Igarashi T;Abel ED;Komuro I
胰岛素样生长因子-1（IGF-1）信号最近被认为与长期耐力训练后心脏肥大的发展有关，其机制可能涉及能量应激。考虑到胰岛素和IGF-1信号的潜在重叠，我们试图确定这两种信号通路是否有助于短期运动训练后运动诱导的心脏肥大。在心脏特异性IGF-1受体（IGF 1 R）敲除小鼠（CIGFRKO）、心脏特异性胰岛素受体（IR）敲除小鼠（CIRKO）、心肌细胞中缺乏一个IR等位基因的CIGFRKO小鼠（IGFR-/-IR+/-）和心肌细胞中缺乏一个IGF 1 R等位基因的CIRKO小鼠（IGFR+/-IR-/-）中进行研究。静脉注射IGF-1或4周内游泳75小时可增加对照组和CIRKO小鼠心脏中IGF 1 R酪氨酸磷酸化水平，但CIGFRKO小鼠则没有。有趣的是，在对照组和CIGFRKO小鼠中，在IGF-1给药或运动训练后，心脏中的IR酪氨酸磷酸化也增加，但在CIRKO小鼠中没有。CIGFRKO和CIRKO小鼠运动训练后的心脏肥大程度与对照小鼠相当。相反，IGFR−/−IR+/−和IGFR+/−IR−/−小鼠的运动诱导的心脏肥大显著减弱。因此，IGF-1和运动激活心脏中的IGF 1 R和IR，IGF 1 R和IR介导的信号可能在心脏对运动训练的肥大反应中起多余的作用。
Insulin-like growth factor-1 (IGF-1) signaling has recently been implicated in the development of cardiac hypertrophy after long-term endurance training, via mechanisms that may involve energetic stress. Given the potential overlap of insulin and IGF-1 signaling we sought to determine if both signaling pathways could contribute to exercise-induced cardiac hypertrophy following shorter-term exercise training. Studies were performed in mice with cardiac-specific IGF-1 receptor (IGF1R) knockout (CIGFRKO), mice with cardiac-specific insulin receptor (IR) knockout (CIRKO), CIGFRKO mice that lacked one IR allele in cardiomyocytes (IGFR−/−IR+/−), and CIRKO mice that lacked one IGF1R allele in cardiomyocytes (IGFR+/−IR−/−). Intravenous administration of IGF-1 or 75 hours of swimming over 4 weeks increased IGF1R tyrosine phosphorylation in the heart in control and CIRKO mice but not in CIGFRKO mice. Intriguingly, IR tyrosine phosphorylation in the heart was also increased following IGF-1 administration or exercise training in control and CIGFRKO mice but not in CIRKO mice. The extent of cardiac hypertrophy following exercise training in CIGFRKO and CIRKO mice was comparable to that in control mice. In contrast, exercise-induced cardiac hypertrophy was significantly attenuated in IGFR−/−IR+/− and IGFR+/−IR−/− mice. Thus, IGF-1 and exercise activates both IGF1R and IR in the heart, and IGF1R- and IR-mediated signals may serve redundant roles in the hypertrophic responses of the heart to exercise training.