Effect of Glucagon-Like Peptide-1 (GLP-1) on Glycemic Control and Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting

Sokos, George; Bolukoglu, Hakki; German, Judy; Hentosz, Teresa; Magovern, George J.; Maher, Thomas D.; Dean, David A.; Bailey, Stephen; Marrone, Gary C.; Benckart, Daniel H.; Elahi, Dariush; Shannon, Richard P.

doi:10.1016/j.amjcard.2007.05.022

Cited by 219 publications

(187 citation statements)

References 21 publications

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“…GLP-1 relaxed femoral artery in a dose-response manner (23), and GLP-1 is associated with vasodilation induced by acetylcholine (24). In humans, the systemic infusion of GLP-1 or its analogs does not induce hypertension but, rather, has protective effects (25,26). Therefore, the increased vascular resistance demonstrated by the present data seems to be specific for brain GLP-1 signaling and not observed in response to a systemic infusion.…”

Section: Discussionmentioning

confidence: 54%

Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity

et al. 2008

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OBJECTIVE-To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular function. GLP-1 is also produced in the brain, where its contribution to central regulation of metabolic and cardiovascular homeostasis remains incompletely understood.RESEARCH DESIGN AND METHODS-Awake free-moving mice were infused with the GLP-1 receptor agonist exendin-4 (Ex4) into the lateral ventricle of the brain in the basal state or during hyperinsulinemic eu-/hyperglycemic clamps. Arterial femoral blood flow, whole-body insulin-stimulated glucose utilization, and heart rates were continuously recorded. RESULTS-A continuous 3-h brain infusion of Ex4 decreasedfemoral arterial blood flow and whole-body glucose utilization in the awake free-moving mouse clamped in a hyperinsulinemichyperglycemic condition, only demonstrating that this effect was strictly glucose dependent. However, the heart rate remained unchanged. The metabolic and vascular effects of Ex4 were markedly attenuated by central infusion of the GLP-1 receptor (GLP-1R) antagonist exendin-9 (Ex9) and totally abolished in GLP-1 receptor knockout mice. A correlation was observed between the metabolic rate and the vascular flow in control and Ex4-infused mice, which disappeared in Ex9 and GLP-1R knockout mice. Moreover, hypothalamic nitric oxide synthase activity and the concentration of reactive oxygen species (ROS) were also reduced in a GLP-1R-dependent manner, whereas the glutathione antioxidant capacity was increased. Central GLP-1 activated vagus nerve activity, and complementation with ROS donor dose-dependently reversed the effect of brain GLP-1 signaling on peripheral blood flow.CONCLUSIONS-Our data demonstrate that central GLP-1 signaling is an essential component of circuits integrating cardiovascular and metabolic responses to hyperglycemia.

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Section: Discussionmentioning

confidence: 54%

Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity

et al. 2008

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“…Sokos et al 20 examined its effect on glycemic control and LV function in patients with known coronary artery disease and preserved LVEF undergoing coronary artery bypass grafting. Twenty patients were divided to receive standard therapy alone compared to standard therapy with GLP-1 (1.5 pmol/kg/min) for 12 hours before surgery and continuing for 48 hours thereafter.…”

Section: Experimental Studies Of Glp-1 In Non-ischemic Dilated Cardiomentioning

confidence: 99%

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

Fields

Patterson

Karnik

et al. 2009

Clinical Cardiology

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Pharmacologic intervention for the failing heart has traditionally targeted neurohormonal activation and ventricular remodeling associated with cardiac dysfunction. Despite the multitude of agents available for the treatment of heart failure, it remains a highly prevalent clinical syndrome with substantial morbidity and mortality, necessitating alternative strategies of targeted management. One such area of interest is the ability to modulate myocardial glucose uptake and its impact on cardioprotection. Glucose‐insulin‐potassium (GIK) infusions have been studied for decades, with conflicting results regarding benefit in acute myocardial infarction. Based on the same concepts, glucagon‐like peptide‐1‐[7–36] amide (GLP‐1) has recently been demonstrated to be a more effective alternative in left ventricular (LV) systolic dysfunction. This paper provides a review on the current evidence supporting the use of GLP‐1 in both animal models and humans with ischemic and nonischemic cardiomyopathy. Copyright © 2009 Wiley Periodicals, Inc.

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“…Mild improvements were observed in some studies [26,27], whereas no significant changes in LVEF were noted in others [28,29] (Table 1).…”

Section: Glp-1 and Cardiac Functionmentioning

confidence: 94%

GLP-1 receptor agonists and heart failure in diabetes

Scheen

2017

Diabetes & Metabolism

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The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR -TIMI 53), whereas a markedly decreased risk was highlighted with the sodium -glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a significant reduction in cardiovascular and all-cause mortality in patients with T2D at risk of cardiovascular disease. These results are reassuring in the face of the somewhat negative results of the FIGHT trial, which evaluated the effects of liraglutide in patients with advanced HF and low LVEF, such that further studies and caution are now required when using this agent to treat such patients in clinical practice.

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Effect of Glucagon-Like Peptide-1 (GLP-1) on Glycemic Control and Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting

Cited by 219 publications

References 21 publications

Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity

Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity

Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control

GLP-1 receptor agonists and heart failure in diabetes

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