Hepatic Glucose Production

Hepatic glucose production (HGP) is the production and release of glucose by the liver into the bloodstream. It is an important part of glucose homeostasis, particularly when glucose is not being absorbed from a recent meal. The liver can supply circulating glucose through two main pathways: glycogenolysis, which mobilizes glucose from stored glycogen, and gluconeogenesis, which synthesizes glucose from noncarbohydrate precursors .^1,2

The relative contribution of these pathways changes with metabolic conditions. During an overnight fast, both hepatic glycogenolysis and gluconeogenesis contribute substantially to glucose output. As fasting continues and liver glycogen stores decline, gluconeogenesis becomes increasingly important. Gluconeogenic precursors include lactate, glycerol, and glucogenic amino acids .^1,2

HGP is strongly regulated by hormones and nutrient availability. Glucagon promotes hepatic glucose output, particularly by rapidly stimulating glycogenolysis, and also promotes gluconeogenesis. Insulin generally suppresses HGP through multiple mechanisms, including promoting glycogen synthesis, inhibiting glycogen breakdown, and reducing gluconeogenic flux through both direct hepatic effects and indirect effects on other tissues. These signals help the liver shift between releasing glucose during fasting and storing or using glucose after food intake .^1,2

Hepatic glucose production is not synonymous with gluconeogenesis. Gluconeogenesis is one biochemical pathway contributing to HGP, while glycogenolysis provides another source of glucose. HGP refers specifically to glucose output from the liver, whereas the broader term endogenous glucose production can also include glucose produced by other organs, particularly the kidneys .¹