Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion

Duna Massillon, Nir Barzilai, Meredith Hawkins, Dina Prus-Wertheimer, Luciano Rossetti

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)153-157
Number of pages5
JournalDiabetes
Volume46
Issue number1
DOIs
StatePublished - Jan 1997

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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