Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 3; pp. H1328 - H1334
• Main Authors: McFalls, Edward O, Hou, MingXiao, Bache, Robert J, Best, Aaron, Marx, David, Sikora, Joseph, Ward, Herbert B
• Format: Journal Article
• Language: English
• Published: United States 01.09.2004
• Subjects: Animals; Biological Transport; Echocardiography; Enzyme Activation; Glucose - metabolism; Glucose Transporter Type 4; Heart - physiopathology; Mitogen-Activated Protein Kinases - metabolism; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Myocardial Stunning - metabolism; Myocardium - enzymology; Myocardium - metabolism; Nitric Oxide Synthase - metabolism; p38 Mitogen-Activated Protein Kinases; Swine; Time Factors
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01188.2003

1 Division of Cardiology, Veterans Affairs Medical Center, and 2 Division of Cardiology, University of Minnesota, Minneapolis, Minnesota 55417 Submitted 12 December 2003 ; accepted in final form 23 April 2004 In preconditioned myocardium, activation of the mitogen-activated protein kinase (MAPK) p38 leads to increased glucose uptake via enhanced GLUT-4 translocation. Glucose uptake is also increased in chronic hibernating myocardium, but the role of p38 MAPK and GLUT-4 translocation has not been studied. Nine swine underwent instrumentation of the proximal left anterior descending coronary artery (LAD) with a small, external constrictor. At 3 mo after instrumentation, myocardial glucose uptake by PET imaging was higher in the LAD than in the remote region under basal, fasted conditions (0.08 ± 0.02 vs. 0.04 ± 0.01 µmol·min –1 ·g –1 , P < 0.05). Compared with the remote region, the LAD region demonstrated increased membrane-bound GLUT-4 relative to total content (61 ± 04 vs. 45 ± 06%, P < 0.05), higher glycogen (28.37 ± 4.41 vs. 19.26 ± 1.87 mg/g wet wt, P < 0.05), and increased inducible nitric oxide synthase (NOS) activity (1.43 ± 0.34 vs. 0.51 ± 0.21 activity/mg protein, P < 0.05). p38 MAPK was 47 ± 14% higher in the LAD than in the remote region ( P < 0.05) and correlated well with the absolute degree of GLUT-4 membrane-bound translocation ( r = 0.81, P < 0.01), relative increase in glycogen ( r = 0.70, P < 0.05), and total NOS activity ( r = 0.68, P < 0.05). In chronic hibernating myocardial tissue, p38 MAPK activation is increased under basal fasted conditions and correlates well with the increased degree of GLUT-4 translocation, glycogen accumulation, and NOS activity. As in preconditioned myocardium, activation of p38 MAPK may play an important role in the metabolic adaptations that characterize chronic hibernating myocardium. GLUT-4; glucose uptake; preconditioned myocardium; inducible nitric oxide synthase Address for reprint requests and other correspondence: E. O. McFalls, Cardiology (111C), VA Medical Center, 1 Veterans Dr., Minneapolis, MN 55417 (E-mail: mcfal001{at}tc.umn.edu ).