Target intelligence / Profile preview

Hepatic Gluconeogenesis

Molecular classification
Metabolic Pathway
01

Overview

Hepatic gluconeogenesis is a metabolic pathway in the liver that synthesizes glucose from non-carbohydrate precursors, playing a critical role in maintaining blood glucose levels during fasting, starvation, low-carbohydrate diets, or intense exercise. It converts substrates like lactate, glycerol, and glucogenic amino acids into glucose via key enzymes including Pyruvate Carboxylase (PC), Phosphoenolpyruvate Carboxykinase (PEPCK), Fructose-1,6-bisphosphatase (FBPase), and Glucose-6-phosphatase (G6PC). The pathway is regulated by hormones such as glucagon, insulin, and cortisol, and transcription factors like CRTC2. Dysregulation leads to excessive hepatic glucose production, a hallmark of fasting hyperglycemia seen in diabetes mellitus. Targeting regulators has shown promise in reducing hyperglycemia experimentally.

Other names
Liver GluconeogenesisHepatic Glucose Production
02

Mechanism of action

Hepatic gluconeogenesis is a target for reducing excessive glucose production in diabetes. Approaches include inhibiting key enzymes (PC, PEPCK, FBPase, G6PC) or modulating transcriptional regulators (CRTC2, CREB, Sam68) involved in the pathway.

03

Biological functions

Glucose homeostasisBlood glucose regulationEnergy metabolismSubstrate cycle
04

Disease associations

Type 2 Diabetes MellitusHyperglycemiaInsulin Resistance
05

Safety considerations

Hypoglycemia (with excessive inhibition)Lactic acidosis (with Metformin)Drug-induced liver injury
06

Interacting drugs

Metformin (indirectly)

2 more in the full profile.

07

Biomarkers

Fasting blood glucoseHbA1cPlasma glucose levelsInsulin levels

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