Journal
CIRCULATION
Volume 110, Issue 8, Pages 955-961Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000139339.85840.DD
Keywords
cardiomyopathy; insulin; ventricles; glucose
Funding
- NIA NIH HHS [AG-023125] Funding Source: Medline
- NIDA NIH HHS [DA-10480] Funding Source: Medline
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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 < 0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group. 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.
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