9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Glucagon-Like Peptide-1 : A Promising Agent for Cardioprotection During Myocardial Ischemia

      review-article
      , BM, BSc a , b , , BSc b , , MD b , , MA, DM a ,
      JACC: Basic to Translational Science
      Elsevier
      GLP-1, glucagon-like peptide-1, ischemia reperfusion injury, ischemic heart disease, percutaneous coronary intervention, ATP, adenosine triphosphate, ANP, atrial natriuretic peptide, AMI, acute myocardial infarction, DPP, dipeptidyl-peptidase, GLP-1, glucagon-like peptide 1-(7-36) amide, GLP-1R, GLP-1 receptor, GLP-1RA, GLP-1 receptor agonist, IC, ischemic conditioning, IR, ischemia reperfusion, PCI, percutaneous coronary intervention, RISK, reperfusion injury survival kinase, SAFE, survivor-activating factor enhancement, STEMI, ST-segment elevation myocardial infarction

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Glucagon-like peptide-1-(7-36) amide (GLP-1) is a human incretin hormone responsible for the release of insulin in response to food. Pre-clinical and human physiological studies have demonstrated cardioprotection from ischemia-reperfusion injury. It can reduce infarct size, ischemic left ventricular dysfunction, and myocardial stunning. GLP-1 receptor agonists have also been shown to reduce infarct size in myocardial infarction. The mechanism through which this protection occurs is uncertain but may include hijacking the subcellular pathways of ischemic preconditioning, modulation of myocardial metabolism, and hemodynamic effects including peripheral, pulmonary, and coronary vasodilatation. This review will assess the evidence for each of these mechanisms in turn. Challenges remain in successfully translating cardioprotective interventions from bench-to-bedside. The window of cardioprotection is short and timing of cardioprotection in the appropriate clinical setting is critically important. We will emphasize the need for high-quality, well-designed research to evaluate GLP-1 as a cardioprotective agent for use in real-world practice.

          Related collections

          Most cited references57

          • Record: found
          • Abstract: found
          • Article: not found

          Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways.

          The glucagon-like peptide 1 receptor (GLP-1R) is believed to mediate glucoregulatory and cardiovascular effects of the incretin hormone GLP-1(7-36) (GLP-1), which is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to GLP-1(9-36), a truncated metabolite generally thought to be inactive. Novel drugs for the treatment of diabetes include analogues of GLP-1 and inhibitors of DPP-4; however, the cardiovascular effects of distinct GLP-1 peptides have received limited attention. Here, we show that endothelium and cardiac and vascular myocytes express a functional GLP-1R as GLP-1 administration increased glucose uptake, cAMP and cGMP release, left ventricular developed pressure, and coronary flow in isolated mouse hearts. GLP-1 also increased functional recovery and cardiomyocyte viability after ischemia-reperfusion injury of isolated hearts and dilated preconstricted arteries from wild-type mice. Unexpectedly, many of these actions of GLP-1 were preserved in Glp1r(-/-) mice. Furthermore, GLP-1(9-36) administration during reperfusion reduced ischemic damage after ischemia-reperfusion and increased cGMP release, vasodilatation, and coronary flow in wild-type and Glp1r(-/-) mice, with modest effects on glucose uptake. Studies using a DPP-4-resistant GLP-1R agonist and inhibitors of DPP-4 and nitric oxide synthase showed that the effects of GLP-1(7-36) were partly mediated by GLP-1(9-36) through a nitric oxide synthase-requiring mechanism that is independent of the known GLP-1R. These data describe cardioprotective actions of GLP-1(7-36) mediated through the known GLP-1R and novel cardiac and vascular actions of GLP-1(7-36) and its metabolite GLP-1(9-36) independent of the known GLP-1R. Our data suggest that the extent to which GLP-1 is metabolized to GLP-1(9-36) may have functional implications in the cardiovascular system.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion.

            Glucose-insulin-potassium infusions are beneficial in uncomplicated patients with acute myocardial infarction (AMI) but are of unproven efficacy in AMI with left ventricular (LV) dysfunction because of volume requirements associated with glucose infusion. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties that stimulate glucose uptake without the requirements for concomitant glucose infusion. We investigated the safety and efficacy of a 72-hour infusion of GLP-1 (1.5 pmol/kg per minute) added to background therapy in 10 patients with AMI and LV ejection fraction (EF) 1.63+/-0.09, P 2.02+/-0.11, P<0.01) compared with control subjects. The benefits of GLP-1 were independent of AMI location or history of diabetes. GLP-1 was well tolerated, with only transient gastrointestinal effects. When added to standard therapy, GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mechanisms of action of glucagon-like peptide 1 in the pancreas.

              Glucagon-like peptide 1 (GLP-1) is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate, and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past 20 years culminating in a naturally occurring GLP-1 receptor (GLP-1R) agonist, exendin 4 (Ex-4), now being used to treat type 2 diabetes mellitus (T2DM). GLP-1 engages a specific guanine nucleotide-binding protein (G-protein) coupled receptor (GPCR) that is present in tissues other than the pancreas (brain, kidney, lung, heart, and major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1R activation, adenylyl cyclase (AC) is activated and cAMP is generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the protein kinase A (PKA) and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1R activation also increases insulin synthesis, beta cell proliferation, and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in T2DM patients treated with Ex-4. This review will focus on the effects resulting from GLP-1R activation in the pancreas.
                Bookmark

                Author and article information

                Contributors
                Journal
                JACC Basic Transl Sci
                JACC Basic Transl Sci
                JACC: Basic to Translational Science
                Elsevier
                2452-302X
                27 June 2016
                June 2016
                27 June 2016
                : 1
                : 4
                : 267-276
                Affiliations
                [a ]Department of Interventional Cardiology, Papworth Hospital, Cambridge, United Kingdom
                [b ]Department of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
                Author notes
                [] Reprint requests and correspondence: Dr. Stephen P. Hoole, Papworth Hospital, Department of Interventional Cardiology, Lakeside Crescent, Papworth Everard, Cambridge, Cambs CB23 3RE, United Kingdom. stephen.hoole@ 123456papworth.nhs.uk
                Article
                S2452-302X(16)30020-1
                10.1016/j.jacbts.2016.03.011
                6113423
                30167515
                18c33fe1-a869-4470-8929-d80c4df1166b
                © 2016 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 January 2016
                : 28 March 2016
                : 31 March 2016
                Categories
                STATE-OF-THE-ART REVIEW

                glp-1,glucagon-like peptide-1,ischemia reperfusion injury,ischemic heart disease,percutaneous coronary intervention,atp, adenosine triphosphate,anp, atrial natriuretic peptide,ami, acute myocardial infarction,dpp, dipeptidyl-peptidase,glp-1, glucagon-like peptide 1-(7-36) amide,glp-1r, glp-1 receptor,glp-1ra, glp-1 receptor agonist,ic, ischemic conditioning,ir, ischemia reperfusion,pci, percutaneous coronary intervention,risk, reperfusion injury survival kinase,safe, survivor-activating factor enhancement,stemi, st-segment elevation myocardial infarction

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content168

                Cited by14

                Most referenced authors1,480