title: Exendin-4 attenuates cardiac hypertrophy via AMPK/mTOR signaling pathway activation.
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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Zhongshan Medical College of Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation Ministry of Health, Guangzhou 510080, China. Electronic address: hejiangui1964@yeah.net.
authors.forename: Jiangui
authors.initials: J
authors.lastname: He
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020123:Sirolimus
keywords: AMPK; Cardiac hypertrophy; Exendin-4; GLP-1