Preconditioning enhanced glucose uptake is mediated by p38 MAP kinase not by phosphatidylinositol 3-kinase

Haiyan Tong, Weina Chen, Robert E. London, Elizabeth Murphy, Charles Steenbergen

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Ischemia is reported to stimulate glucose uptake, but the signaling pathways involved are poorly understood. Modulation of glucose transport could be important for the cardioprotective effects of brief intermittent periods of ischemia and reperfusion, termed ischemic preconditioning. Previous work indicates that preconditioning reduces production of acid and lactate during subsequent sustained ischemia, consistent with decreased glucose utilization. However, there are also data that preconditioning enhances glucose uptake. The present study examines whether preconditioning alters glucose transport and whether this is mediated by either phosphatidylinositol 3-kinase (PI3K) or p38 MAP kinase. Langendorff-perfused rat hearts were preconditioned with 4 cycles of 5 min of ischemia and 5 min of reperfusion, with glucose as substrate. During the last reflow, glucose was replaced with 5 mM acetate and 5 mM 2-deoxyglucose (2DG), and hexose transport was measured from the rate of production of 2-deoxyglucose 6- phosphate (2DG6P), using 31P nuclear magnetic resonance. Preconditioning stimulated 2DG uptake; after 15 min of perfusion with 2DG, 2DG6P levels were 165% of initial ATP in preconditioned hearts compared with 96% in control hearts (p < 0.05). Wortmannin, an inhibitor of PI3K, did not block the preconditioning induced stimulation of 2DG6P production, but perfusion with SB202190, an inhibitor of p38 MAP kinase, did attenuate 2DG6P accumulation (111% of initial ATP, p < 0.05 compared with preconditioned hearts). SB202190 had no effect on 2DG6P accumulation in nonpreconditioned hearts. Preconditioning stimulation of translocation of GLUT4 to the plasma membrane was not inhibited by wortmannin. The data demonstrate that ischemic preconditioning increases hexose transport and that this is mediated by p38 MAP kinase and is PI3K-independent.

Original languageEnglish (US)
Pages (from-to)11981-11986
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number16
DOIs
StatePublished - Apr 21 2000

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Phosphatidylinositol 3-Kinase
p38 Mitogen-Activated Protein Kinases
Glucose
Deoxyglucose
Ischemia
Ischemic Preconditioning
Hexoses
Reperfusion
Perfusion
Adenosine Triphosphate
Mitogen-Activated Protein Kinase 1
Cell membranes
Rats
Lactic Acid
Acetates
Magnetic Resonance Spectroscopy
Cell Membrane
Nuclear magnetic resonance
Modulation
2-deoxyglucose-6-phosphate

ASJC Scopus subject areas

  • Biochemistry

Cite this

Preconditioning enhanced glucose uptake is mediated by p38 MAP kinase not by phosphatidylinositol 3-kinase. / Tong, Haiyan; Chen, Weina; London, Robert E.; Murphy, Elizabeth; Steenbergen, Charles.

In: Journal of Biological Chemistry, Vol. 275, No. 16, 21.04.2000, p. 11981-11986.

Research output: Contribution to journalArticle

Tong, Haiyan ; Chen, Weina ; London, Robert E. ; Murphy, Elizabeth ; Steenbergen, Charles. / Preconditioning enhanced glucose uptake is mediated by p38 MAP kinase not by phosphatidylinositol 3-kinase. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 16. pp. 11981-11986.
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