Gluconeogenesis signaling pathway (GNG)

The **gluconeogenesis signaling pathway** is a series of coordinated biochemical reactions that result in the synthesis of glucose from non-carbohydrate precursors, mainly in the liver, but also in kidney and intestine[5][1]. The pathway becomes active during fasting, starvation, intense exercise, or metabolic stress to maintain blood glucose levels. Key enzymes involved include pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6PC)[5][1]. The pathway is tightly regulated by hormonal (insulin suppresses, glucagon and cortisol stimulate) and transcriptional mechanisms (FoxO1, PGC-1α, SIRT1)[5][8][6]. Dysregulation of gluconeogenesis contributes to the pathogenesis of type 2 diabetes and other metabolic disorders[2][8]. While several drugs target gluconeogenesis indirectly (notably metformin), the pathway as a whole is not a druggable entity; instead, specific enzymes or regulators within the pathway are considered valid therapeutic targets[1][5][8].

Other names

GluconeogenesisHepatic gluconeogenesisGlucose biosynthesis pathway

Inhibition or activation of pathway enzymes (e.g., PEPCK, G6PC, FBPase, pyruvate carboxylase); Modulation of transcriptional regulators (e.g., FoxO1, PGC-1α); Modulation of upstream hormone signaling (insulin inhibits, glucagon stimulates)