Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts.

Abstract

Recent evidence suggests that glucagon-like peptide-1 (GLP-1) enhances recovery of left ventricular (LV) function after transient coronary artery occlusion. However, it is uncertain whether GLP-1 has direct effects on normal or ischemic myocardium and whether the mechanism involves increased myocardial glucose uptake. LV function and myocardial glucose uptake and lactate production were measured under basal conditions and after 30 min of low-flow ischemia and 30 min of reperfusion in the presence and absence of GLP-1-(7-36) amide. The response was compared with standard buffer alone or buffer containing insulin (100 microU/ml). GLP-1 decreased the left ventricular developed pressure (baseline: 100 +/- 2 mm Hg; GLP-1: 75 +/- 3 mm Hg, p < 0.05) and LV dP/dt (baseline: 4876 +/- 65 mm Hg/s; GLP-1: 4353 +/- 76 mm Hg/s, p < 0.05) in normal hearts. GLP-1 increased myocardial glucose uptake (baseline: 33 +/- 3 micromol/min/g; GLP-1: 81 +/- 7 micromol/min/g, p < 0.05) by increasing nitric oxide production and glucose transporter (GLUT)-1 translocation. GLP-1 enhanced recovery after 30 min of low-flow ischemia with significant improvements in LV end-diastolic pressure (control: 13 +/- 4 mm Hg; GLP-1: 3 +/- 2 mm Hg, p < 0.05) and LV developed pressure (control: 66 +/- 6 mm Hg; GLP-1: 98 +/- 5 mm Hg, p < 0.05). GLP-1 increased LV function, myocardial glucose uptake, and GLUT-1 and GLUT-4 translocation during reperfusion to an extent similar to that with insulin. GLP-1 has direct effects on the normal heart, reducing contractility, but increasing myocardial glucose uptake through a non-Akt-1-dependent mechanism, distinct from the actions of insulin. However, GLP-1 increased myocardial glucose uptake and enhanced recovery of cardiac function after low-flow ischemia in a fashion similar to that of insulin.

• Authors: Tingcun Zhao, Pratik Parikh, Siva Bhashyam, Hakki Bolukoglu, Indu Poornima, You-Tang Shen, Richard P Shannon
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 317 Issue 3 Pg. 1106-13 (Jun 2006) ISSN: 0022-3565 [Print] United States
• PMID: 16489128 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Glucose Transporter Type 1
• Peptide Fragments
• Slc2a1 protein, rat
• glucagon-like peptide 1 (7-36)amide
• Nitric Oxide
• Glucagon-Like Peptides
• Glucagon-Like Peptide 1
• Glucagon
• Glucose

Topics

• Animals
• Glucagon (pharmacology)
• Glucagon-Like Peptide 1
• Glucagon-Like Peptides (pharmacology)
• Glucose (metabolism)
• Glucose Transporter Type 1 (metabolism)
• Heart (drug effects)
• In Vitro Techniques
• Male
• Myocardial Contraction (drug effects)
• Myocardial Ischemia (metabolism, physiopathology)
• Myocardium (metabolism)
• Nitric Oxide (metabolism)
• Peptide Fragments (pharmacology)
• Protein Transport
• Rats
• Rats, Wistar
• Ventricular Function, Left (drug effects)