Exendin-4 attenuates cardiac hypertrophy via AMPK/mTOR signaling pathway activation

Yue Zhou, Xin He, Yili Chen, Yiyi Huang, Lingling Wu, Jiangui He

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Diabetes mellitus is a prominent risk factor for cardiovascular diseases. Diabetic cardiomyopathy is an important complication of the heart independent of hypertension and coronary artery disease and is accompanied by cardiac hypertrophy. Cardiac hypertrophy easily leads to heart failure, which is a leading cause of morbidity and mortality. Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which has various beneficial roles in the cardiovascular system, and exendin-4 is a highly potent glucagon-like peptide 1 receptor agonist. However, the role of GLP-1 in cardiac hypertrophy remains unknown. Our study revealed that exendin-4 treatment ameliorated phenylephrine (PE)-induced cardiac hypertrophy, which presented as decreased cardiac hypertrophic markers (ANP, BNP, and β-MHC) and cell surface area. This condition was significantly reversed upon treatment with the GLP-1 receptor antagonist exendin9-39. We also discovered that Erk1/2 and AMPK signaling pathways were involved in this process. Furthermore, our data demonstrate that the AMPK inhibitor compound C inhibited the anti-hypertrophic effect of exendin-4, which is associated with the mTOR/p70S6K/4-EBP1 signaling pathway. Finally, exendin-4 enhanced the anti-hypertrophic effect of rapamycin. In summary, our study disclosed that exedin-4 inhibits cardiac hypertrophy by upregulating GLP-1 receptor expression and activating the AMPK/mTOR signaling pathway.

Original languageEnglish
Pages (from-to)394-399
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume468
Issue number1-2
DOIs
StatePublished - 4 Dec 2015
Externally publishedYes

Keywords

  • AMPK
  • Cardiac hypertrophy
  • Exendin-4
  • GLP-1

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