TY - JOUR
T1 - Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion
AU - Massillon, Duna
AU - Barzilai, Nir
AU - Hawkins, Meredith
AU - Prus-Wertheimer, Dina
AU - Rossetti, Luciano
PY - 1997/1
Y1 - 1997/1
N2 - The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) complex. The recently cloned catalytic unit of this complex has been shown to be regulated by insulin, dexamethasone, cAMP, and glucose. Using a combination of intralipid and/or nicotinic acid infusions and a pancreatic clamp technique, we maintained plasma free fatty acids (FFAs) at three different levels (0.26 ± 0.07, 0.56 ± 0.09, and 1.59 ± 0.12 mmol/l) in the presence of well-controlled hormonal and metabolic conditions. An increase in the plasma FFA concentration within the physiological range caused a rapid, greater than threefold increase in the mRNA and protein levels of the catalytic subunit of Glc-6-Pase in the liver. These data indicate that the in vive gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein.
AB - The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) complex. The recently cloned catalytic unit of this complex has been shown to be regulated by insulin, dexamethasone, cAMP, and glucose. Using a combination of intralipid and/or nicotinic acid infusions and a pancreatic clamp technique, we maintained plasma free fatty acids (FFAs) at three different levels (0.26 ± 0.07, 0.56 ± 0.09, and 1.59 ± 0.12 mmol/l) in the presence of well-controlled hormonal and metabolic conditions. An increase in the plasma FFA concentration within the physiological range caused a rapid, greater than threefold increase in the mRNA and protein levels of the catalytic subunit of Glc-6-Pase in the liver. These data indicate that the in vive gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein.
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U2 - 10.2337/diab.46.1.153
DO - 10.2337/diab.46.1.153
M3 - Article
C2 - 8971097
AN - SCOPUS:0031031276
SN - 0012-1797
VL - 46
SP - 153
EP - 157
JO - Diabetes
JF - Diabetes
IS - 1
ER -