Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy

Nikolaidis, Lazaros A.; Elahi, Dariush; Shen, You-Tang; Shannon, Richard P.

doi:10.1152/ajpheart.00347.2005

Cited by 274Diabetes Treatment and ManagementCardiovascular Function and Risk FactorsHeart Failure Treatment and Management

Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy

Nikolaidis, Lazaros A., Elahi, Dariush, Shen, You-Tang, Shannon, Richard P.·2005·American Journal of Physiology-Heart and Circulatory Physiology

DOI 10.1152/ajpheart.00347.2005

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Abstract

We have shown previously that the glucagon-like peptide-1 (GLP-1)-(7–36) amide increases myocardial glucose uptake and improves left ventricular (LV) and systemic hemodynamics in both conscious dogs with pacing-induced dilated cardiomyopathy (DCM) and humans with LV systolic dysfunction after acute myocardial infarction. However, GLP-1-(7–36) is rapidly degraded in the plasma to GLP-1-(9–36) by dipeptidyl peptidase IV (DPP IV), raising the issue of which peptide is the active moiety. By way of methodology, we compared the efficacy of a 48-h continuous intravenous infusion of GLP-1-(7–36) (1.5 pmol·kg−1·min−1) to GLP-1-(9–36) (1.5 pmol·kg−1·min−1) in 28 conscious, chronically instrumented dogs with pacing-induced DCM by measuring LV function and transmyocardial substrate uptake under basal and insulin-stimulated conditions using hyperinsulinemic-euglycemic clamps. As a result, dogs with DCM demonstrated myocardial insulin resistance under basal and insulin-stimulated conditions. Both GLP-1-(7–36) and GLP-1-(9–36) significantly reduced ( P < 0.01) LV end-diastolic pressure [GLP-1-(7–36), 28 ± 1 to 15 ± 2 mmHg; GLP-1-(9–36), 29 ± 2 to 16 ± 1 mmHg] and significantly increased ( P < 0.01) the first derivative of LV pressure [GLP-1-(7–36), 1,315 ± 81 to 2,195 ± 102 mmHg/s; GLP-1-(9–36), 1,336 ± 77 to 2,208 ± 68 mmHg] and cardiac output [GLP-1-(7–36), 1.5 ± 0.1 to 1.9 ± 0.1 l/min; GLP-1-(9–36), 2.0 ± 0.1 to 2.4 ± 0.05 l/min], whereas an equivolume infusion of saline had no effect. Both peptides increased myocardial glucose uptake but without a significant increase in plasma insulin. During the GLP-1-(9–36) infusion, negligible active (NH 2-terminal) peptide was measured in the plasma. In conclusion, in DCM, GLP-1-(9–36) mimics the effects of GLP-1-(7–36) in stimulating myocardial glucose uptake and improving LV and systemic hemodynamics through insulinomimetic as opposed to insulinotropic effects. These data suggest that GLP-1-(9–36) amide is an active peptide.

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GLP-1 agonists improve cardiac output and blood pressure in dogs with pacing-induced cardiomyopathy.
“GLP-1 agonists improve cardiac output and blood pressure (BP) in dogs with pacing-induced cardiomyopathy (28).”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [28]

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Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake via p38 MAP Kinase–Mediated, Nitric Oxide–Dependent Mechanisms in Conscious Dogs With Dilated Cardiomyopathy
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Authors: Nikolaidis, L. A., Elahi, D., Shen, Y.-T., & Shannon, R. P.
Affiliations: Allegheny General Hospital (US)
ORCID: Nikolaidis, Lazaros A.
Venue: American Journal of Physiology-Heart and Circulatory Physiology
Publisher: American Physiological Society
Published: 2005-12
Volume: 289
Issue: 6
Pages: H2401-H2408
ISSN: 0363-6135 (ISSN-L)
1522-1539
DOI: 10.1152/ajpheart.00347.2005
OpenAlex: W2169976140
Cited by: 274
References: 27
Citations by year: 2025: 4 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 19 · 2015: 15 · 2014: 29 · 2013: 22 · 2012: 26
FWCI: 6.37
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (7r01da010480-09, 5r01ag023125-05)
National Institute on Aging (AG-023125)
National Institute on Drug Abuse (DA 10480)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords: glucagon-like peptide-1, GLP-1(7-36), dipeptidyl peptidase IV, dilated cardiomyopathy, pacing-induced cardiomyopathy, myocardial glucose uptake, myocardial insulin resistance, left ventricular function, hemodynamics, cardiac output, myocardial substrate metabolism, hyperinsulinemic-euglycemic clamp
MeSH terms: Animals, Blood Pressure, Cardiomyopathy, Dilated, Consciousness, Coronary Circulation, Dogs, Dose-Response Relationship, Drug, Glucagon-Like Peptides, Female, Glucagon, Glucose, Heart, Heart Ventricles, Male, Myocardium, Peptide Fragments, Peptides, Stroke Volume, Treatment Outcome, Ventricular Dysfunction, Left, Glucagon-Like Peptide 1

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Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy

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