Incretin-mediated control of cardiac energy metabolism

in Journal of Endocrinology
Authors:
Jordan S F Chan Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
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
Current site
Google Scholar
PubMed Close
https://orcid.org/0009-0006-1567-8772
,
Tanin Shafaati Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada

Search for other papers by Tanin Shafaati in
Current site
Google Scholar
PubMed Close
, and
John R Ussher Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
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
Current site
Google Scholar
PubMed Close
https://orcid.org/0000-0001-9574-5707

Correspondence should be addressed to J R Ussher: jussher@ualberta.ca

This paper forms part of a special collection on Incretins. The guest editors for this collection were Timo D Müller and Erin Mulvihill.

DOI:
https://doi.org/10.1530/JOE-24-0011
Volume/Issue:
Volume 263: Issue 1
Article Type:
Review Article
Article ID:
e240011
Online Publication Date:
08 Aug 2024
Copyright:
© the author(s) 2024
Restricted access
Rent on DeepDyve

Sign up for journal news

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) are incretin hormones that stimulate insulin secretion and improve glycemic control in individuals with type 2 diabetes (T2D). Data from several cardiovascular outcome trials for GLP-1 receptor (GLP-1R) agonists have demonstrated significant reductions in the occurrence of major adverse cardiovascular events in individuals with T2D. Although the cardiovascular actions attributed to GLP-1R agonism have been extensively studied, little is known regarding the cardiovascular consequences attributed to GIP receptor (GIPR) agonism. As there is now an increasing focus on the development of incretin-based co-agonist therapies that activate both the GLP-1R and GIPR, it is imperative that we understand the mechanism(s) through which these incretins impact cardiovascular function. This is especially important considering that cardiovascular disease represents the leading cause of death in individuals with T2D. With increasing evidence that perturbations in cardiac energy metabolism are a major contributor to the pathology of diabetes-related cardiovascular disease, this may represent a key component through which GLP-1R and GIPR agonism influence cardiovascular outcomes. Not only do GIP and GLP-1 increase the secretion of insulin, they may also modify glucagon secretion, both of which have potent actions on cardiac substrate utilization. Herein we will discuss the potential direct and indirect actions through which GLP-1R and GIPR agonism impact cardiac energy metabolism while interrogating the evidence to support whether such actions may account for incretin-mediated cardioprotection in T2D.

Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 78 78 42
PDF Downloads 106 106 52

 

  • Collapse
  • Expand
Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2024
Article ID:
e240011
Article Type:
Review Article
Received Date:
15 Jan 2024
Accepted Date:
16 Jul 2024
Print Publication Date:
01 Oct 2024
Online Publication Date:
08 Aug 2024
Keywords:
cardiac energy metabolism; cardiovascular disease; glucose-dependent insulinotropic polypeptide; glucose-dependent insulinotropic polypeptide receptor; glucagon-like peptide 1; glucagon-like peptide-1 receptor; incretins

  • Ali S, Ussher JR, Baggio LL, Kabir MG, Charron MJ, Ilkayeva O, Newgard CB & & Drucker DJ 2015 Cardiomyocyte glucagon receptor signaling modulates outcomes in mice with experimental myocardial infarction. Molecular Metabolism 4 132–143. (https://doi.org/10.1016/j.molmet.2014.11.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Almutairi M, Al Batran R & & Ussher JR 2019 Glucagon-like peptide-1 receptor action in the vasculature. Peptides 111 26–32. (https://doi.org/10.1016/j.peptides.2018.09.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Almutairi M, Gopal K, Greenwell AA, Young A, Gill R, Aburasayn H, Al Batran R, Chahade JJ, Gandhi M, Eaton F, et al.2021 The GLP-1 receptor agonist liraglutide increases myocardial glucose oxidation rates via indirect mechanisms and mitigates experimental diabetic cardiomyopathy. Canadian Journal of Cardiology 37 140–150. (https://doi.org/10.1016/j.cjca.2020.02.098)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Aravindhan K, Bao W, Harpel MR, Willette RN, Lepore JJ & & Jucker BM 2015 Cardioprotection resulting from glucagon-like Peptide-1 administration involves shifting metabolic substrate utilization to increase energy efficiency in the rat heart. PLoS One 10 e0130894. (https://doi.org/10.1371/journal.pone.0130894)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Baggio LL & & Drucker DJ 2007 Biology of incretins: GLP-1 and GIP. Gastroenterology 132 2131–2157. (https://doi.org/10.1053/j.gastro.2007.03.054)

  • Baggio LL, Yusta B, Mulvihill EE, Cao X, Streutker CJ, Butany J, Cappola TP, Margulies KB & & Drucker DJ 2018 GLP-1 receptor expression within the human heart. Endocrinology 159 1570–1584. (https://doi.org/10.1210/en.2018-00004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ & & Husain M 2008 Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation 117 2340–2350. (https://doi.org/10.1161/CIRCULATIONAHA.107.739938)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bao W, Aravindhan K, Alsaid H, Chendrimada T, Szapacs M, Citerone DR, Harpel MR, Willette RN, Lepore JJ & & Jucker BM 2011 Albiglutide, a long lasting glucagon-like peptide-1 analog, protects the rat heart against ischemia/reperfusion injury: evidence for improving cardiac metabolic efficiency. PLoS One 6 e23570. (https://doi.org/10.1371/journal.pone.0023570)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Battiprolu PK, Hojayev B, Jiang N, Wang ZV, Luo X, Iglewski M, Shelton JM, Gerard RD, Rothermel BA, Gillette TG, et al.2012 Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice. Journal of Clinical Investigation 122 1109–1118. (https://doi.org/10.1172/JCI60329)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Brownsey RW, Boone AN & & Allard MF 1997 Actions of insulin on the mammalian heart: metabolism, pathology and biochemical mechanisms. Cardiovascular Research 34 3–24. (https://doi.org/10.1016/s0008-6363(9700051-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Campbell JE & & Drucker DJ 2013 Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metabolism 17 819–837. (https://doi.org/10.1016/j.cmet.2013.04.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Campbell JE, Ussher JR, Mulvihill EE, Kolic J, Baggio LL, Cao X, Liu Y, Lamont BJ, Morii T, Streutker CJ, et al.2016 TCF1 links GIPR signaling to the control of beta cell function and survival. Nature Medicine 22 84–90. (https://doi.org/10.1038/nm.3997)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chai W, Dong Z, Wang N, Wang W, Tao L, Cao W & & Liu Z 2012 Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes 61 888–896. (https://doi.org/10.2337/db11-1073)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chan JSF, Greenwell AA, Saed CT, Stenlund MJ, Mangra-Bala IA, Tabatabaei Dakhili SA, Yang K, Ferrari SR, Eaton F, Gopal K & & Ussher JR 2024 Liraglutide alleviates experimental diabetic cardiomyopathy in a PDH-dependent manner. Journal of Endocrinology 262 e240032. (https://doi.org/10.1530/JOE-24-0032)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cunningham CH, Lau JY, Chen AP, Geraghty BJ, Perks WJ, Roifman I, Wright GA & & Connelly KA 2016 Hyperpolarized 13C metabolic MRI of the human heart: initial experience. Circulation Research 119 1177–1182. (https://doi.org/10.1161/CIRCRESAHA.116.309769)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, Hu FB, Kahn CR, Raz I, Shulman GI, et al.2015 Type 2 diabetes mellitus. Nature Reviews. Disease Primers 1 15019. (https://doi.org/10.1038/nrdp.2015.19)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Drucker DJ 2016 The cardiovascular biology of glucagon-like peptide-1. Cell Metabolism 24 15–30. (https://doi.org/10.1016/j.cmet.2016.06.009)

  • Dunlay SM, Givertz MM, Aguilar D, Allen LA, Chan M, Desai AS, Deswal A, Dickson VV, Kosiborod MN, Lekavich CL, et al.2019 Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America: this statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation 140 e294–e324. (https://doi.org/10.1161/CIR.0000000000000691)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, et al.2002 The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. Journal of Clinical Investigation 109 121–130. (https://doi.org/10.1172/JCI14080)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K & SURPASS-2 Investigators 2021 Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. New England Journal of Medicine 385 503–515. (https://doi.org/10.1056/NEJMoa2107519)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, et al.2019 Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394 121–130. (https://doi.org/10.1016/S0140-6736(1931149-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, Pratley R, Lopes RD, Lam CSP, Khurmi NS, Heenan L, Del Prato S, et al.2021 Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. New England Journal of Medicine 385 896–907. (https://doi.org/10.1056/NEJMoa2108269)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gopal K, Almutairi M, Al Batran R, Eaton F, Gandhi M & & Ussher JR 2018 Cardiac-specific deletion of pyruvate dehydrogenase impairs glucose oxidation rates and induces diastolic dysfunction. Frontiers in Cardiovascular Medicine 5 17. (https://doi.org/10.3389/fcvm.2018.00017)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gopal K, Al Batran R, Altamimi TR, Greenwell AA, Saed CT, Tabatabaei Dakhili SA, Dimaano MTE, Zhang Y, Eaton F, Sutendra G, et al.2021 FoxO1 inhibition alleviates type 2 diabetes-related diastolic dysfunction by increasing myocardial pyruvate dehydrogenase activity. Cell Reports 35 108935. (https://doi.org/10.1016/j.celrep.2021.108935)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Greenwell AA, Tabatabaei Dakhili SA, Wagg CS, Saed CT, Chan JSF, Yang K, Mangra-Bala IA, Stenlund MJ, Eaton F, Gopal K, et al.2024 Pharmacological inhibition of succinyl coenzyme A:3-ketoacid coenzyme A transferase alleviates the progression of diabetic cardiomyopathy. Journal of the American Heart Association 13 e032697. (https://doi.org/10.1161/JAHA.123.032697)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Heather LC, Gopal K, Srnic N & & Ussher JR 2024 Redefining diabetic cardiomyopathy: perturbations in substrate metabolism at the heart of its pathology. Diabetes 73 659–670. (https://doi.org/10.2337/dbi23-0019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, et al.2022 Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet. Diabetes and Endocrinology 10 418–429. (https://doi.org/10.1016/S2213-8587(2200085-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hernandez AF, Green JB, Janmohamed S, D'Agostino RB Sr, Granger CB, Jones NP, Leiter LA, Rosenberg AE, Sigmon KN, Somerville MC, et al.2018 Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392 1519–1529. (https://doi.org/10.1016/S0140-6736(1832261-X)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Holst JJ 2007 The physiology of glucagon-like peptide 1. Physiological Reviews 87 1409–1439. (https://doi.org/10.1152/physrev.00034.2006)

  • Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, et al.2022 Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine 387 205–216. (https://doi.org/10.1056/NEJMoa2206038)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kahn SE, Cooper ME & & Del Prato S 2014 Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383 1068–1083. (https://doi.org/10.1016/S0140-6736(1362154-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H & & Al Kaabi J 2020 Epidemiology of type 2 diabetes - global burden of disease and forecasted trends. Journal of Epidemiology and Global Health 10 107–111. (https://doi.org/10.2991/jegh.k.191028.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kim M, Platt MJ, Shibasaki T, Quaggin SE, Backx PH, Seino S, Simpson JA & & Drucker DJ 2013 GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nature Medicine 19 567–575. (https://doi.org/10.1038/nm.3128)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Moller DV, et al.2023 Semaglutide in patients with heart failure with preserved ejection fraction and obesity. New England Journal of Medicine 389 1069–1084. (https://doi.org/10.1056/NEJMoa2306963)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Le Page LM, Rider OJ, Lewis AJ, Ball V, Clarke K, Johansson E, Carr CA, Heather LC & & Tyler DJ 2015 Increasing pyruvate dehydrogenase flux as a treatment for diabetic cardiomyopathy: a combined 13C hyperpolarized magnetic resonance and echocardiography study. Diabetes 64 2735–2743. (https://doi.org/10.2337/db14-1560)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lepore JJ, Olson E, Demopoulos L, Haws T, Fang Z, Barbour AM, Fossler M, Davila-Roman VG, Russell SD & & Gropler RJ 2016 Effects of the novel long-acting GLP-1 agonist, albiglutide, on cardiac function, cardiac metabolism, and exercise capacity in patients with chronic heart failure and reduced ejection fraction. JACC. Heart Failure 4 559–566. (https://doi.org/10.1016/j.jchf.2016.01.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lopaschuk GD, Witters LA, Itoi T, Barr R & & Barr A 1994 Acetyl-CoA carboxylase involvement in the rapid maturation of fatty acid oxidation in the newborn rabbit heart. Journal of Biological Chemistry 269 25871–25878. (https://doi.org/10.1016/S0021-9258(1847327-9)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lopaschuk GD, Folmes CDL & & Stanley WC 2007 Cardiac energy metabolism in obesity. Circulation Research 101 335–347. (https://doi.org/10.1161/CIRCRESAHA.107.150417)

  • Lopaschuk GD, Ussher JR, Folmes CDL, Jaswal JS & & Stanley WC 2010 Myocardial fatty acid metabolism in health and disease. Physiological Reviews 90 207–258. (https://doi.org/10.1152/physrev.00015.2009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lopaschuk GD, Karwi QG, Ho KL, Pherwani S & & Ketema EB 2020 Ketone metabolism in the failing heart. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids 1865 158813. (https://doi.org/10.1016/j.bbalip.2020.158813)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lopaschuk GD, Karwi QG, Tian R, Wende AR & & Abel ED 2021 Cardiac energy metabolism in heart failure. Circulation Research 128 1487–1513. (https://doi.org/10.1161/CIRCRESAHA.121.318241)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Madrazo JA & & Kelly DP 2008 The PPAR trio: regulators of myocardial energy metabolism in health and disease. Journal of Molecular and Cellular Cardiology 44 968–975. (https://doi.org/10.1016/j.yjmcc.2008.03.021)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, et al.2016a Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine 375 1834–1844. (https://doi.org/10.1056/NEJMoa1607141)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, et al.2016b Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 375 311–322. (https://doi.org/10.1056/NEJMoa1603827)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • McLean BA, Wong CK, Kabir MG & & Drucker DJ 2022 Glucagon-like Peptide-1 receptor Tie2+ cells are essential for the cardioprotective actions of liraglutide in mice with experimental myocardial infarction. Molecular Metabolism 66 101641. (https://doi.org/10.1016/j.molmet.2022.101641)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, et al.2002 Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nature Medicine 8 738–742. (https://doi.org/10.1038/nm727)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Moberly SP, Mather KJ, Berwick ZC, Owen MK, Goodwill AG, Casalini ED, Hutchins GD, Green MA, Ng Y, Considine RV, et al.2013 Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus. Basic Research in Cardiology 108 365. (https://doi.org/10.1007/s00395-013-0365-x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mulvihill EE & & Drucker DJ 2014 Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocrine Reviews 35 992–1019. (https://doi.org/10.1210/er.2014-1035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D & & Shannon RP 2004a Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 109 962–965. (https://doi.org/10.1161/01.CIR.0000120505.91348.58)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT & & Shannon RP 2004b Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 110 955–961. (https://doi.org/10.1161/01.CIR.0000139339.85840.DD)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nikolaidis LA, Elahi D, Shen YT & & Shannon RP 2005 Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. American Journal of Physiology. Heart and Circulatory Physiology 289 H2401–H2408. (https://doi.org/10.1152/ajpheart.00347.2005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Noyan-Ashraf MH, Shikatani EA, Schuiki I, Mukovozov I, Wu J, Li RK, Volchuk A, Robinson LA, Billia F, Drucker DJ, et al.2013 A glucagon-like peptide-1 analog reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity. Circulation 127 74–85. (https://doi.org/10.1161/CIRCULATIONAHA.112.091215)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Patel MS & & Korotchkina LG 2006 Regulation of the pyruvate dehydrogenase complex. Biochemical Society Transactions 34 217–222. (https://doi.org/10.1042/BST20060217)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Patel MS, Nemeria NS, Furey W & & Jordan F 2014 The pyruvate dehydrogenase complexes: structure-based function and regulation. Journal of Biological Chemistry 289 16615–16623. (https://doi.org/10.1074/jbc.R114.563148)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Peterson LR, Soto PF, Herrero P, Mohammed BS, Avidan MS, Schechtman KB, Dence C & & Gropler RJ 2008 Impact of gender on the myocardial metabolic response to obesity. JACC. Cardiovascular Imaging 1 424–433. (https://doi.org/10.1016/j.jcmg.2008.05.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Poornima I, Brown SB, Bhashyam S, Parikh P, Bolukoglu H & & Shannon RP 2008 Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat. Circulation. Heart Failure 1 153–160. (https://doi.org/10.1161/CIRCHEARTFAILURE.108.766402)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P & Clinical Guidelines Committee of the American College of Physicians 2012 Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American college of physicians. Annals of Internal Medicine 156 218–231. (https://doi.org/10.7326/0003-4819-156-3-201202070-00011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Richards P, Parker HE, Adriaenssens AE, Hodgson JM, Cork SC, Trapp S, Gribble FM & & Reimann F 2014 Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes 63 1224–1233. (https://doi.org/10.2337/db13-1440)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rider OJ, Apps A, Miller J, Lau JYC, Lewis AJM, Peterzan MA, Dodd MS, Lau AZ, Trumper C, Gallagher FA, et al.2020 Noninvasive in vivo assessment of cardiac metabolism in the healthy and diabetic human heart using hyperpolarized (13)C MRI. Circulation Research 126 725–736. (https://doi.org/10.1161/CIRCRESAHA.119.316260)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ritchie RH & & Abel ED 2020 Basic mechanisms of diabetic heart disease. Circulation Research 126 1501–1525. (https://doi.org/10.1161/CIRCRESAHA.120.315913)

  • Siraj MA, Mundil D, Beca S, Momen A, Shikatani EA, Afroze T, Sun X, Liu Y, Ghaffari S, Lee W, et al.2020 Cardioprotective GLP-1 metabolite prevents ischemic cardiac injury by inhibiting mitochondrial trifunctional protein-α. Journal of Clinical Investigation 130 1392–1404. (https://doi.org/10.1172/JCI99934)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sivertsen J, Rosenmeier J, Holst JJ & & Vilsboll T 2012 The effect of glucagon-like peptide 1 on cardiovascular risk. Nature Reviews. Cardiology 9 209–222. (https://doi.org/10.1038/nrcardio.2011.211)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sun Q, Guven B, Wagg CS, Almeida de Oliveira A, Silver H, Zhang L, Chen B, Wei K, Ketema EB, Karwi QG, et al.2024 Mitochondrial fatty acid oxidation is the major source of cardiac adenosine triphosphate production in heart failure with preserved ejection fraction. Cardiovascular Research 120 360–371. (https://doi.org/10.1093/cvr/cvae006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tabatabaei Dakhili SA, Greenwell AA & & Ussher JR 2023 Pyruvate dehydrogenase complex and glucose oxidation as a therapeutic target in diabetic heart disease. Journal of Lipid and Atherosclerosis 12 47–57. (https://doi.org/10.12997/jla.2023.12.1.47)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Taegtmeyer H, Young ME, Lopaschuk GD, Abel ED, Brunengraber H, Darley-Usmar V, Des Rosiers C, Gerszten R, Glatz JF, Griffin JL, et al.2016 Assessing cardiac metabolism: a scientific statement from the American heart association. Circulation Research 118 1659–1701. (https://doi.org/10.1161/RES.0000000000000097)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR 2014 Deciphering ventricular GLP-1 action: time for a change of heart. American Journal of Physiology. Heart and Circulatory Physiology 307 H1390–H1392. (https://doi.org/10.1152/ajpheart.00680.2014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR & & Drucker DJ 2014 Cardiovascular actions of incretin-based therapies. Circulation Research 114 1788–1803. (https://doi.org/10.1161/CIRCRESAHA.114.301958)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR & & Drucker DJ 2023 Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nature Reviews. Cardiology 20 463–474. (https://doi.org/10.1038/s41569-023-00849-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR, Koves TR, Jaswal JS, Zhang L, Ilkayeva O, Dyck JRB, Muoio DM & & Lopaschuk GD 2009 Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase. Diabetes 58 1766–1775. (https://doi.org/10.2337/db09-0011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR, Sutendra G & & Jaswal JS 2012 The impact of current and novel anti-diabetic therapies on cardiovascular risk. Future Cardiology 8 895–912. (https://doi.org/10.2217/fca.12.68)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR, Fillmore N, Keung W, Mori J, Beker DL, Wagg CS, Jaswal JS & & Lopaschuk GD 2014a Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice. Canadian Journal of Cardiology 30 940–944. (https://doi.org/10.1016/j.cjca.2014.04.023)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR, Baggio LL, Campbell JE, Mulvihill EE, Kim M, Kabir MG, Cao X, Baranek BM, Stoffers DA, Seeley RJ, et al.2014b Inactivation of the cardiomyocyte glucagon-like peptide-1 receptor (GLP-1R) unmasks cardiomyocyte-independent GLP-1R-mediated cardioprotection. Molecular Metabolism 3 507–517. (https://doi.org/10.1016/j.molmet.2014.04.009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR, Elmariah S, Gerszten RE & & Dyck JRB 2016 The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease. Journal of the American College of Cardiology 68 2850–2870. (https://doi.org/10.1016/j.jacc.2016.09.972)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ussher JR, Campbell JE, Mulvihill EE, Baggio LL, Bates HE, McLean BA, Gopal K, Capozzi M, Yusta B, Cao X, et al.2018 Inactivation of the glucose-dependent insulinotropic polypeptide receptor improves outcomes following experimental myocardial infarction. Cell Metabolism 27 450–460.e6. (https://doi.org/10.1016/j.cmet.2017.11.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wong CK, Yusta B, Koehler JA, Baggio LL, McLean BA, Matthews D, Seeley RJ & & Drucker DJ 2022 Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation. Cell Metabolism 34 1514–1531.e7. (https://doi.org/10.1016/j.cmet.2022.08.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhao T, Parikh P, Bhashyam S, Bolukoglu H, Poornima I, Shen YT & & Shannon RP 2006 Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts. Journal of Pharmacology and Experimental Therapeutics 317 1106–1113. (https://doi.org/10.1124/jpet.106.100982)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhao P, Zhang J, Yin XG, Maharaj P, Narraindoo S, Cui LQ & & Tang YS 2013 The effect of trimetazidine on cardiac function in diabetic patients with idiopathic dilated cardiomyopathy. Life Sciences 92 633–638. (https://doi.org/10.1016/j.lfs.2012.03.015)

    • PubMed
    • Search Google Scholar
    • Export Citation