Recombinant Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake and Improves Left Ventricular Performance in Conscious Dogs With Pacing-Induced Dilated Cardiomyopathy
- 24 August 2004
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 110 (8), 955-961
- https://doi.org/10.1161/01.cir.0000139339.85840.dd
Abstract
Background— The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake. Methods and Results— Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol · kg −1 · min −1 ). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant ( P Conclusions— rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.Keywords
This publication has 17 references indexed in Scilit:
- Glucagon-Like Peptide-1 Augments Insulin-Mediated Glucose Uptake in the Obese StateJournal of Clinical Endocrinology & Metabolism, 2002
- Impaired Myocardial Fatty Acid Oxidation and Reduced Protein Expression of Retinoid X Receptor-α in Pacing-Induced Heart FailureCirculation, 2002
- Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neuronsJCI Insight, 2002
- The Insulinotropic Effect of Acute Exendin-4 Administered to Humans: Comparison of Nondiabetic State to Type 2 DiabetesJournal of Clinical Endocrinology & Metabolism, 2002
- Glucagon-Like Peptide-1Proceedings of the 1972 Laurentian Hormone Conference, 2001
- Effects of infusion of glucose-insulin-potassium on myocardial function after a recent myocardial infarctionActa Cardiologica, 2000
- Insulin Resistance in Chronic Heart FailureJournal of Cardiovascular Pharmacology, 2000
- Insulin Resistance in Chronic Heart Failure: Relation to Severity and Etiology of Heart FailureJournal of the American College of Cardiology, 1997
- Total-body and myocardial substrate oxidation in congestive heart failureMetabolism, 1994
- Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failureMetabolism, 1991