Regulation of myocardial glucose uptake and transport during ischemia and energetic stress.
Myocardial glucose utilization increases in response to the energetic stress imposed on the heart by exercise, pressure overload, and myocardial ischemia. Recruitment of glucose transport proteins is the cellular mechanism by which the heart increases glucose transport for subsequent metabolism. Moderate regional ischemia leads to the translocation of both glucose transporters, GLUT4 and GLUT1, to the sarcolemma in vivo. Myocardial ischemia also stimulates 5'-adenosine monophosphate-activated protein kinase, which may be a fuel gauge in the heart and other tissues signaling the need to turn on energy-generating metabolic pathways. Pharmacologic stimulation of this kinase increases cardiac glucose uptake and transporter translocation, suggesting that it may play an important role in augmenting glucose entry in the setting of ischemic or energetic stress. Thus, recent work has provided insight into the cellular and molecular mechanisms responsible for glucose uptake during energetic stress, which may lead to new approaches to the treatment of patients with coronary artery disease.
Young
L H
LH
Department of Internal Medicine and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Russell
R R
RR
Yin
R
R
Caplan
M J
MJ
Ren
J
J
Bergeron
R
R
Shulman
G I
GI
Sinusas
A J
AJ
D000249:Adenosine Monophosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; D000249:Adenosine Monophosphate; D000263:Adenylate Kinase; D005947:Glucose