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Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction
- Title
- Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction
- Authors
- 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.
- Ewha Authors
- 김민석
- SCOPUS Author ID
- 김민석
- Issue Date
- 2018
- Journal Title
- CELL METABOLISM
- ISSN
- 1550-4131
1932-7420
- Citation
- CELL METABOLISM vol. 27, no. 2, pp. 450 - +
- Publisher
- CELL PRESS
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.1016/j.cmet.2017.11.003
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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