Liraglutide alleviates diabetic cardiomyopathy by blocking CHOP‑triggered apoptosis via the inhibition of the IRE-α pathway

Ji,Yuqiang; Zhao,Zhao; Cai,Tianzhi; Yang,Pengkang; Cheng,Manli

doi:10.3892/mmr.2014.1956

Liraglutide alleviates diabetic cardiomyopathy by blocking CHOP‑triggered apoptosis via the inhibition of the IRE-α pathway

Authors:
- Yuqiang Ji
- Zhao Zhao
- Tianzhi Cai
- Pengkang Yang
- Manli Cheng
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Affiliations: Department of Cardiovascular Medicine, First Hospital of Xi'an, Xi'an, Shaanxi 710002, P.R. China, Department of Cardiovascular Medicine, The Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China
Published online on: February 17, 2014 https://doi.org/10.3892/mmr.2014.1956
Pages: 1254-1258

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Abstract

Clinically, diabetes mellitus is closely associated with and induces certain cardiovascular diseases. The aim of this study was to investigate endoplasmic reticulum (ER) stress-associated apoptosis of diabetic cardiomyopathy (DCM), and explore the protective mechanism of liraglutide. The DCM model was established with a high-fat diet and streptozotocin (STZ). Cardiac function was detected by echocardiogram examination and hematoxylin-eosin staining. ER stress unfolded protein response (UPR) hallmarks [inositol-requiring enzyme‑α (IRE-α), p-Perk and ATF6] and transcription factors were detected with western blotting. Apoptosis inducers CHOP, c-Jun amino terminal kinase (JNK) and casapse-12 were also examined with western blotting. The results indicated that liraglutide is capable of improving cardiac function in DCM rats (P<0.05). IRE-α expression was significantly increased in the DCM group compared with the control group (P<0.05), and liraglutide is capable of decreasing IRE-α expression. X-box transcription factor-1 (XBP-1) was significantly spliced in the model group, and downregulated in the liraglutide-treated group. CHOP protein was upregulated in the DCM group, but inactivated by liraglutide treatment. In conclusion, liraglutide is capable of protecting DCM and blocking CHOP-mediated ER stress by inhibiting the IRE-α UPR pathway.

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