Search Results
You are looking at 1 - 1 of 1 items for
- Author: Amanda A Greenwell x
- Refine by access: All content x
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Jordan S F Chan in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Amanda A Greenwell in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Christina T Saed in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Magnus J Stenlund in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Indiresh A Mangra-Bala in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Seyed Amirhossein Tabatabaei Dakhili in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Kunyan Yang in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Sally R Ferrari in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Farah Eaton in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by Keshav Gopal in
Google Scholar
PubMed
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
Search for other papers by John R Ussher in
Google Scholar
PubMed
Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist used for the treatment of T2D, has been shown to alleviate diabetic cardiomyopathy (DbCM) in experimental T2D, which was associated with increased myocardial glucose oxidation. To determine whether this increase in glucose oxidation is necessary for cardioprotection, we hypothesized that liraglutide’s ability to alleviate DbCM would be abolished in mice with cardiomyocyte-specific deletion of pyruvate dehydrogenase (PDH; Pdha1 CM−/− mice), the rate-limiting enzyme of glucose oxidation. Male Pdha1 CM−/− mice and their α-myosin heavy chain Cre expressing littermates (αMHCCre mice) were subjected to experimental T2D via 10 weeks of high-fat diet supplementation, with a single low-dose injection of streptozotocin (75 mg/kg) provided at week 4. All mice were randomized to treatment with either vehicle control or liraglutide (30 µg/kg) twice daily during the final 2.5 weeks, with cardiac function assessed via ultrasound echocardiography. As expected, liraglutide treatment improved glucose homeostasis in both αMHCCre and Pdha1 CM−/− mice with T2D, in the presence of mild weight loss. Parameters of systolic function were unaffected by liraglutide treatment in both αMHCCre and Pdha1 CM−/− mice with T2D. However, liraglutide treatment alleviated diastolic dysfunction in αMHCCre mice, as indicated by an increase and decrease in the e′/a′ and E/e′ ratios, respectively. Conversely, liraglutide failed to rescue these indices of diastolic dysfunction in Pdha1 CM−/− mice. Our findings suggest that increases in glucose oxidation are necessary for GLP-1R agonist mediated alleviation of DbCM. As such, strategies aimed at increasing PDH activity may represent a novel approach for the treatment of DbCM.