Hepatic gluconeogenesis and systemic glucose–lipid metabolism

Hepatic gluconeogenesis and systemic glucose–lipid metabolism refer to the integrated physiological processes by which the liver and other tissues regulate blood sugar levels and lipid distribution to maintain energy homeostasis. Hepatic gluconeogenesis is the metabolic pathway that results in the generation of glucose from non-carbohydrate substrates, such as lactate, glycerol, and glucogenic amino acids, primarily during periods of fasting (PubMed: 23564431). Systemic glucose–lipid metabolism encompasses the broader coordination of glucose uptake, storage, and oxidation alongside fatty acid synthesis and breakdown across various organs (PubMed: 1904957). Dysregulation of these pathways is a primary driver of metabolic disorders, including type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease (NAFLD) (PubMed: 28276250). Therapeutic intervention in these processes typically involves targeting specific molecular components such as the enzyme glucose-6-phosphatase, the energy sensor AMPK, or hormonal receptors like the insulin and glucagon receptors (PubMed: 24450930). Because this entry describes a broad physiological process rather than a single molecular entity, it is classified as a pathway rather than a specific therapeutic target.

Other names

Hepatic glucose productionGlucose-lipid metabolic axisEndogenous glucose productionSystemic energy homeostasis

Drugs modulate this process by inhibiting rate-limiting gluconeogenic enzymes (e.g., PEPCK, G6Pase), activating energy-sensing proteins like AMPK, or enhancing insulin sensitivity to suppress hepatic glucose output (PubMed: 24450930).