TY - JOUR
T1 - Effect of glyburide on myocardial metabolism and function
AU - Schaffer, Stephen W.
AU - Tan, Boen H.
AU - Mozaffari, Mahmood S
N1 - Funding Information:
From the Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama. This work was supported by grants from the National Institutes of Health (HL-28445) and the Upjohn Company. Requests for reprints should be addressed to Dr. Stephen W. Schaffer, Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama 36688.
PY - 1985/9/20
Y1 - 1985/9/20
N2 - Exposure of perfused rat hearts to the second-generation sulfonylurea glyburide led to a dramatic increase in glycolytic flux and lactate production. Maximal response in the absence of insulin occurred at a concentration of 2.8 μM and resulted in a 45 percent increase in the glucose utilization rate. When insulin was included in the buffer, glyburide response was significantly increased. Similarly, glyburide potentiated the metabolic effects of insulin. Since glyburide did not promote glycogenolysis, the increase in glycolysis was caused solely by the rise in glucose utilization. The classic cross-over plot for glycolytic intermediates and transport showed that glyburide stimulates glycolysis by activating the rate-limiting enzyme phosphofructokinase and promoting glucose transport. Glycolytic intermediate data also suggested that the sulfonylurea promotes oxidation of pyruvate via the citric acid cycle. Since the drug does not alter oxygen consumption, the contribution of glucose to overall adenosine triphosphate production rises while that of fatty acids falls. These metabolic changes aid the heart in resisting an ischemic insult.
AB - Exposure of perfused rat hearts to the second-generation sulfonylurea glyburide led to a dramatic increase in glycolytic flux and lactate production. Maximal response in the absence of insulin occurred at a concentration of 2.8 μM and resulted in a 45 percent increase in the glucose utilization rate. When insulin was included in the buffer, glyburide response was significantly increased. Similarly, glyburide potentiated the metabolic effects of insulin. Since glyburide did not promote glycogenolysis, the increase in glycolysis was caused solely by the rise in glucose utilization. The classic cross-over plot for glycolytic intermediates and transport showed that glyburide stimulates glycolysis by activating the rate-limiting enzyme phosphofructokinase and promoting glucose transport. Glycolytic intermediate data also suggested that the sulfonylurea promotes oxidation of pyruvate via the citric acid cycle. Since the drug does not alter oxygen consumption, the contribution of glucose to overall adenosine triphosphate production rises while that of fatty acids falls. These metabolic changes aid the heart in resisting an ischemic insult.
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U2 - 10.1016/S0002-9343(85)80007-3
DO - 10.1016/S0002-9343(85)80007-3
M3 - Article
C2 - 3931461
AN - SCOPUS:0022341482
SN - 0002-9343
VL - 79
SP - 48
EP - 52
JO - The American Journal of Medicine
JF - The American Journal of Medicine
IS - 3 SUPPL. 2
ER -