TY - JOUR
T1 - Endotoxin increases the liver fructose 2,6-bisphosphate concentration in fasted rats
AU - Miller, Bonnie C.
AU - Ishikawa, Emi
AU - Uyeda, Kosaku
AU - Cottam, G. Larry
N1 - Funding Information:
Severe bacterial infection induces a hypermetabolic state in the host that is characterized by an abnormal pattern of carbohydrate metabolism. Rapid mobilization of glycogen stores results in transient hyperglycemia lasting one to several hours (2,3). Subsequently, a progressive and potentially fatal hypoglycemia develops (45) which is attributed to increased glycolysis in peripheral tissues and impaired liver gluconeogenesis. Administration of bacterial endotoxin (e.g., lipopolysaccharide) to experimental animals elicits essentially all of the symptoms of gram negative bacteremia including disruption of glucose homeostasis (6). A 3 to 4-fold increase in carbohydrate flux through phosphofructokinase in hepatocytes, measured 18 hours following endotoxin administration to rats, was recently suggested to be the site of inhibition of hepatic gluconeogenesis by bacterial endotoxin (1). There was no significant difference in carbohydrate flux through *This work was supported in part by Grants DK16194 and CA43311 from the National Institutes of Health and the Research Service of the Veterans Administration.
PY - 1989/12/30
Y1 - 1989/12/30
N2 - Following endotoxin administration to fasted rats, the liver fructose 2,6-bisphosphate level is significantly increased within 1 hr, is elevated 2.3-fold by 3 hrs, and remains elevated 2 to 3-fold for at least 24 hrs. This increase in the potent allosteric activator of phosphofructokinase occurs when there is no change in the liver Glc 6-P, glycogen or cAMP concentrations, or in the activities of phosphoenolpyruvate carboxykinase or pyruvate kinase. The increase in fructose 2,6-bisphosphate concentration accounts for the increased phosphofructokinase activity previously observed in hepatocytes isolated 18 hours following endotoxin administration to rats (1). By stimulating the phosphofructokinase/Fru 1,6-bisphosphate cycle in the direction of glycolysis, fructose 2,6-bisphosphate is likely the factor responsible for decreased gluconeogenesis in endotoxemia.
AB - Following endotoxin administration to fasted rats, the liver fructose 2,6-bisphosphate level is significantly increased within 1 hr, is elevated 2.3-fold by 3 hrs, and remains elevated 2 to 3-fold for at least 24 hrs. This increase in the potent allosteric activator of phosphofructokinase occurs when there is no change in the liver Glc 6-P, glycogen or cAMP concentrations, or in the activities of phosphoenolpyruvate carboxykinase or pyruvate kinase. The increase in fructose 2,6-bisphosphate concentration accounts for the increased phosphofructokinase activity previously observed in hepatocytes isolated 18 hours following endotoxin administration to rats (1). By stimulating the phosphofructokinase/Fru 1,6-bisphosphate cycle in the direction of glycolysis, fructose 2,6-bisphosphate is likely the factor responsible for decreased gluconeogenesis in endotoxemia.
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U2 - 10.1016/0006-291X(89)92711-3
DO - 10.1016/0006-291X(89)92711-3
M3 - Article
C2 - 2558647
AN - SCOPUS:0024842994
SN - 0006-291X
VL - 165
SP - 1072
EP - 1078
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -