Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis

Diabetes Metab Res Rev. Jul-Aug 2001;17(4):250-72. doi: 10.1002/dmrr.217.


Hepatic glycogen is replenished during the absorptive period postprandially. This repletion is prompted partly by an increased hepatic uptake of glucose by the liver, partly by metabolite and hormonal signals in the portal vein, and partly by an increased gluconeogenic flux to glycogen (glyconeogenesis). There is some evidence that the direct formation of glycogen from glucose and that formed by gluconeogenic pathways is linked. This includes: (i) the inhibition of all glycogen synthesis, in vivo, when gluconeogenic flux is blocked by inhibitors; (ii) a dual relationship between glucose concentrations, lactate uptake by the liver and glycogen synthesis (by both pathways) which indicates that glucose sets the maximal rates of glycogen synthesis while lactate uptake determines the actual flux rate to glycogen; (iii) the decrease of both gluconeogenesis and glycogen synthesis by the biguanide, metformin; and (iv) correlations between increased gluconeogenesis and liver glycogen in obese patients and animal models. The degree to which the liver extracts portal glucose is not entirely agreed upon although a preponderance of evidence points to about a 5% extraction rate, following meals, which is dependent on a stimulation of glucokinase. This enzyme may be linked to the expression of other enzymes in the gluconeogenic pathway. Perivenous cells in the liver may induce additional gluconeogenesis in the periportal cells by increasing glycolytically produced lactate. A number of potential mechanisms therefore exist which could link glycogen synthesis from glucose and gluconeogenic substrate.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism
  • Food
  • Glucokinase / metabolism
  • Gluconeogenesis*
  • Glucose / biosynthesis
  • Glucose / metabolism*
  • Glucose Intolerance
  • Glucose-6-Phosphatase / metabolism
  • Glycogen / biosynthesis*
  • Glycogen / metabolism
  • Homeostasis*
  • Humans
  • Liver / metabolism*


  • Glycogen
  • Glucokinase
  • Glucose-6-Phosphatase
  • Glucose