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http://purl.uniprot.org/citations/26259714http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26259714http://www.w3.org/2000/01/rdf-schema#comment"

Background

Type 2 diabetes mellitus (T2DM) worsens the outcome after myocardial infarction (MI). Here, we hypothesized that inhibition of dipeptidyl peptidase-4 (DPP-4) improves survival after MI in T2DM by modifying autophagy in the non-infarcted region of the heart.

Methods and results

Under baseline conditions, there was no significant difference between levels of myocardial autophagy marker proteins in OLETF, a rat model of T2DM, and in LETO, a non-diabetic control. However, in contrast to the response in LETO, LC3-II protein and LC3-positive autophagosomes in the non-infarcted region of the myocardium were not increased after MI in OLETF. The altered autophagic response in OLETF was associated with lack of AMPK/ULK-1 activation, attenuated response of Akt/mTOR/S6 signaling and increased Beclin-1-Bcl-2 interaction after MI. Treatment with vildagliptin (10 mg/kg/day s.c.), a DPP-4 inhibitor, suppressed Beclin-1-Bcl-2 interaction and increased both LC3-II protein level and autophagosomes in the non-infarcted region in OLETF, though it did not normalize AMPK/ULK-1 or mTOR/S6 signaling. Plasma insulin level, but not glucose level, was significantly reduced by vildagliptin at the dose used in this study. Survival rate at 48 h after MI was significantly lower in OLETF than in LETO (32 vs. 82%), despite similar infarct sizes. Vildagliptin improved the survival rate in OLETF to 80%, the benefit of which was abrogated by chloroquine, an autophagy inhibitor.

Conclusions

The results indicate that vildagliptin reduces T2DM-induced increase in post-MI acute mortality possibly by restoring the autophagic response through attenuation of Bcl-2-Beclin-1 interaction."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.org/dc/terms/identifier"doi:10.1186/s12933-015-0264-6"xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Miki T."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Miura T."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Yano T."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Nishizawa K."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Ogasawara M."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Kuno A."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Ishikawa S."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Tanno M."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Murase H."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Kouzu H."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/author"Tobisawa T."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/name"Cardiovasc Diabetol"xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/pages"103"xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/title"Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats."xsd:string
http://purl.uniprot.org/citations/26259714http://purl.uniprot.org/core/volume"14"xsd:string
http://purl.uniprot.org/citations/26259714http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26259714
http://purl.uniprot.org/citations/26259714http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26259714
http://purl.uniprot.org/uniprot/#_A6HLV4-mappedCitation-26259714http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26259714
http://purl.uniprot.org/uniprot/#_A6HLV5-mappedCitation-26259714http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26259714
http://purl.uniprot.org/uniprot/#_P14740-mappedCitation-26259714http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26259714
http://purl.uniprot.org/uniprot/P14740http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/26259714
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