Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease

Read, Philip A.; Khan, Fakhar Z.; Dutka, David P.

doi:10.1136/hrt.2010.219345

Cited by 102 publications

(78 citation statements)

References 34 publications

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“…Sokos et al (34) reported that a long-term infusion of GLP-1 improves both LV ejection fraction and functional capacity in human patients with advanced heart failure (34). This is in agreement with another pilot study showing that treatment with GLP-1 improved LV function in patients with coronary artery disease (28).…”

Section: Discussionsupporting

confidence: 78%

Exendin-4 induces myocardial protection through MKK3 and Akt-1 in infarcted hearts

Zhang

Wang

et al. 2016

American Journal of Physiology-Cell Physiology

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-We have demonstrated that glucagon like peptide-1 (GLP-1) protects the heart against ischemic injury. However, the physiological mechanism by which GLP-1 receptor (GLP-1R) initiates cardioprotection remains to be determined. The objective of this study is to elucidate the functional roles of MAPK kinase 3 (MKK3) and Akt-1 in mediating exendin-4-elicited protection in the infarcted hearts. Adult mouse myocardial infarction (MI) was created by ligation of the left descending artery. Wild-type, MKK3Ϫ/Ϫ , Akt-1 Ϫ/Ϫ , and Akt-1 Ϫ/Ϫ ; MKK3 Ϫ/Ϫ mice were divided into one of several groups: 1) sham: animals underwent thoracotomy without ligation; 2) MI: animals underwent MI and received a daily dose of intraperitoneal injection of vehicle (saline); 3) MI ϩ exendin-4: infarcted mice received daily injections of exendin-4, a GLP-1R agonist (0.1 mg/kg, ip). Echocardiographic measurements indicate that exendin-4 treatment resulted in the preservation of ventricular function and increases in the survival rate, but these effects were diminished in MKK3 Ϫ/Ϫ , Akt-1 Ϫ/Ϫ , and Akt-1 Ϫ/Ϫ ;MKK3 Ϫ/Ϫ mice. Exendin-4 treatments suppressed cardiac hypotrophy and reduced scar size and cardiac interstitial fibrosis, respectively, but these beneficial effects were lost in genetic elimination of MKK3, Akt-1, or Akt-1 Ϫ/Ϫ ;MKK3 Ϫ/Ϫ mice. GLP-1R stimulation stimulated angiogenic responses, which were also mitigated by deletion of MKK3 and Akt-1. Exendin-4 treatment increased phosphorylation of MKK3, p38, and Akt-1 at Ser129 but decreased levels of active caspase-3 and cleaved poly (ADP-ribose) polymerase; these proteins were diminished in MKK3 Ϫ/Ϫ , Akt-1 Ϫ/Ϫ , and Akt-1 Ϫ/Ϫ ; MKK3 Ϫ/Ϫ mice. These results reveal that exendin-4 treatment improves cardiac function, attenuates cardiac remodeling, and promotes angiogenesis in the infarcted myocardium through MKK3 and Akt-1 pathway.glucagon-like peptide-1 receptor; MAPK kinase 3; Akt-1; myocardial infarction; function GLUCAGON-LIKE PEPTIDE-1 (GLP-1) is a naturally occurring incretin that is implicated in the control of appetite and satiety (23). GLP-1 has been studied extensively in type 2 diabetes as a novel insulinotropic peptide whose actions are dependent on the ambient glucose concentration. GLP-1 acts through the GLP-1 receptor (GLP-1R), a 463-amino acid member of the G protein-coupled receptor superfamily (23). GLP-1 is rapidly cleaved by dipeptidyl-peptidase-4 (DPP4), which results in the generation of largely inactive molecular GLP-1 9 -36 amide and GLP-1 9 -37 forms (14). The majority of GLP-1 leaving the intestinal venous circulation has already been cleaved by DPP4 expressed in capillary surrounding gut L cells, which provides an estimated half-life of 1-2 min for intact GLP-1 in vivo (12). The GLP-1 receptor is widely distributed in tissues, including brain, pancreas, intestine, lung, stomach, and kidney. Recently, multiple GLP-1 receptor agonists with longer duration of effect in vivo have been explored, among which is exendin-4, a 39-amino acid peptide that shares 53% sequence ho...

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Section: Discussionsupporting

confidence: 78%

Exendin-4 induces myocardial protection through MKK3 and Akt-1 in infarcted hearts

Zhang

Wang

et al. 2016

American Journal of Physiology-Cell Physiology

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“…33 In coronary artery disease patients with good LV function, a continuous infusion of rGLP-1 for 30 minutes before dobutamine stress echocardiography demonstrated an improved ejection fraction and LV regional wall function as well as mitigated post-ischaemic stunning, predominantly in the ischaemic wall segment. 42 The beneficial effect of a 72-hour GLP-1 infusion on the postinfarction recovery, including an increased ejection fraction and improvement of both global and regional wall motion was also observed in acute myocardial infarction patients with LV ejection fraction of less than 40% after successful primary percutaneous coronary intervention. 43 Long-term GLP-1 infusion also improved myocardial stunning, which was characterised by enhanced LV wall motion and relaxation in I/R dogs.…”

Section: Effects Of Glp-1 On Left Ventricular Functionmentioning

confidence: 99%

Cardioprotective effects of incretin during ischaemia-reperfusion

Chinda

Chattipakorn

2012

Diabetes and Vascular Disease Research

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Incretin is a gut derived peptide hormone secreted in the intestine after food ingestion, and is degraded rapidly after secretion by dipeptidyl peptidase (DPP)-4. Incretin-based therapy, such as glucagon-like peptide (GLP)-1 and the DPP-4 inhibitor, has been proposed as a new therapeutic approach for the treatment of type 2 diabetic patients. In the past few years, growing evidence also demonstrated the cardioprotective effects of incretin-based therapy, especially during ischaemia-reperfusion (I/R) injury in both the animal models and in clinical studies. However, inconsistent reports exist regarding the use of these pharmacological interventions. In this article, a comprehensive review regarding both basic and clinical studies reporting the effects of GLP-1 and DPP-4 inhibitors on I/R hearts is presented and discussed. The consistent findings as well as controversial results are summarised, focusing on the effects of incretin on the infarct size, left ventricular function and haemodynamic improvement during an I/R injury.

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“…73 Acute infusion of GLP-1 (1.2 pmol/kg per minute) 30 minutes before dobutamine stress echocardiography and continuing for 30 minutes into recovery in 14 patients with stable coronary artery disease and normal resting LV function prevented the development of postischemic myocardial dysfunction. 74 Moreover, the infusion of GLP-1 (1.2 pmol/ kg per minute) after completion of the first balloon occlusion reduced LV dysfunction during dual-inflation balloon angioplasty in 20 nondiabetic patients with single-vessel coronary artery disease. 75 Lønborg et al 76 investigated the effects of a 6-hour exenatide or placebo infusion (mean plasma concentration of exenatide was 0.177±0.069 nmol/L) initiated 15 minutes before reperfusion onset in 172 patients undergoing percutaneous coronary intervention to treat ST-segment elevation MI.…”

Section: Clinical Studiesmentioning

confidence: 99%