Regulation of glucose production by the liver

Annu Rev Nutr. 1999;19:379-406. doi: 10.1146/annurev.nutr.19.1.379.


Glucose is an essential nutrient for the human body. It is the major energy source for many cells, which depend on the bloodstream for a steady supply. Blood glucose levels, therefore, are carefully maintained. The liver plays a central role in this process by balancing the uptake and storage of glucose via glycogenesis and the release of glucose via glycogenolysis and gluconeogenesis. The several substrate cycles in the major metabolic pathways of the liver play key roles in the regulation of glucose production. In this review, we focus on the short- and long-term regulation glucose-6-phosphatase and its substrate cycle counter-part, glucokinase. The substrate cycle enzyme glucose-6-phosphatase catalyzes the terminal step in both the gluconeogenic and glycogenolytic pathways and is opposed by the glycolytic enzyme glucokinase. In addition, we include the regulation of GLUT 2, which facilitates the final step in the transport of glucose out of the liver and into the bloodstream.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Gene Expression Regulation
  • Glucokinase / genetics
  • Glucokinase / metabolism
  • Gluconeogenesis
  • Glucose / biosynthesis*
  • Glucose Transporter Type 2
  • Glucose-6-Phosphatase / genetics
  • Glucose-6-Phosphatase / metabolism
  • Glycogen / metabolism
  • Homeostasis*
  • Humans
  • Liver / metabolism*
  • Monosaccharide Transport Proteins / chemistry
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism


  • Blood Glucose
  • Glucose Transporter Type 2
  • Monosaccharide Transport Proteins
  • Glycogen
  • Glucokinase
  • Glucose-6-Phosphatase
  • Glucose