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

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.

• Authors: Yuqiang Ji, Zhao Zhao, Tianzhi Cai, Pengkang Yang, Manli Cheng
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 9 Issue 4 Pg. 1254-8 (Apr 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 24535553 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Ern1 protein, rat
• Multienzyme Complexes
• Transcription Factor CHOP
• Liraglutide
• Glucagon-Like Peptide 1
• Protein Serine-Threonine Kinases
• Endoribonucleases

Topics

• Animals
• Apoptosis (drug effects)
• Blood Glucose (metabolism)
• Diabetic Cardiomyopathies (blood, diagnostic imaging, drug therapy, pathology)
• Disease Models, Animal
• Electrocardiography
• Endoplasmic Reticulum Stress (drug effects)
• Endoribonucleases (metabolism)
• Fasting (blood)
• Glucagon-Like Peptide 1 (analogs & derivatives, pharmacology, therapeutic use)
• Liraglutide
• Male
• Mice
• Multienzyme Complexes (metabolism)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Transcription Factor CHOP
• Ultrasonography