INDUCTION OF HEPATIC GLUCOSE-6-PHOSPHATASE GENE-EXPRESSION BY LIPID INFUSION

The distal enzymatic step in the process of glucose out-put is catalyz ed by the glucose-6-phosphatase (Glc-6-Pase) complex, The recently clo ned catalytic unit of this complex has been shown to be regulated by i nsulin, dexamethasone, cAMP, and glucose, Using a combination of intra lipid and/or nicotinic acid infusions and a pancreatic clamp technique , we maintained plasma free fatty acids (FFAs) at three different leve ls (0.26 +/- 0.07, 0.56 +/- 0.09, and 1.59 +/- 0.12 mmol/l) in the pre sence of well-controlled hormonal and metabolic conditions, An increas e in the plasma FFA concentration within the physiological range cause d a rapid, greater than threefold increase in the mRNA and protein lev els of the catalytic subunit of Glc-6-Pase in the liver, These data in dicate that the in vivo gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that p rolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein.