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首页> 外文期刊>Cell metabolism >Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction
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Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction

机译：葡萄糖依赖性胰岛素的多肽受体的失活改善了实验性心肌梗死后的结果

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摘要

Incretin hormones exert pleiotropic metabolic actions beyond the pancreas. Although the heart expresses both incretin receptors, the cardiac biology of GIP receptor (GIPR) action remains incompletely understood. Here we show that GIPR agonism did not impair the response to cardiac ischemia. In contrast, genetic elimination of the Gipr reduced myocardial infarction (MI)-induced ventricular injury and enhanced survival associated with reduced hormone sensitive lipase (HSL) phosphorylation; it also increased myocardial triacylglycerol (TAG) stores. Conversely, direct GIPR agonism in the isolated heart reduced myocardial TAG stores and increased fatty acid oxidation. The cardioprotective phenotype in Gipr(-/-) mice was partially reversed by pharmacological activation or genetic overexpression of HSL. Selective Gipr inactivation in cardiomyocytes phenocopied Gipr(-/-) mice, resulting in improved survival and reduced adverse remodeling following experimental MI. Hence, the cardiomyocyte GIPR regulates fatty acid metabolism and the adaptive response to ischemic cardiac injury. These findings have translational relevance for developing GIPR-based therapeutics.
机译：Incetin荷尔蒙在胰腺超出胰腺中发挥铅球代谢行动。虽然心脏表达了Incetin受体，但GIP受体的心脏生物学（GIPR）作用仍然不完全理解。在这里，我们表明Gipr激动主义没有损害对心脏缺血的反应。相比之下，GIPR的遗传消除降低了心肌梗死（MI）诱导的心室损伤和增强与激素敏感脂肪酶（HSL）磷酸化相关的存活;它还增加了心肌三酰基甘油（标签）储存。相反，孤立的心脏中的直接Gipr激动症减少了心肌标签储存和增加的脂肪酸氧化。 GIPR（ - / - ）小鼠的心脏保护表型通过HSL的药理学活化或遗传过表达部分反转。在实验MI后，心肌细胞的选择性GIPR失活杂志，导致改善的存活和降低不良重塑。因此，心肌细胞GIPR调节脂肪酸代谢和对缺血性心脏损伤的适应性反应。这些发现具有促进基于GIPR的治疗方法的翻译相关性。

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  • 来源
    《Cell metabolism》 |2018年第2期|共17页
  • 作者

    Ussher John R.; Campbell Jonathan E.; Mulvihill Erin E.; Baggio Laurie L.; Bates Holly E.; McLean Brent A.; Gopal Keshav; Capozzi Megan; Yusta Bernardo; Cao Xiemin; Ali Safina; Kim Minsuk; Kabir M. Golam; Seino Yutaka; Suzuki Jinya; Drucker Daniel J.;

  • 作者单位

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Alberta Fac Pharm &

    Pharmaceut Sci Edmonton AB T6G 2H7 Canada;

    Duke Univ Duke Mol Physiol Inst Med Ctr Durham NC 27701 USA;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

    Kansai Elect Power Hosp 2-1-7 Fukushima Ku Osaka 5530003 Japan;

    Univ Fukui Fac Med Sci Fukui 9101193 Japan;

    Univ Toronto Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada;

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  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
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