title: Novel concepts in insulin regulation of hepatic gluconeogenesis.
abstract: The regulation of hepatic gluconeogenesis is an important process in the adjustment of the blood glucose level, and pathological changes in the glucose production of the liver are a central characteristic in type 2 diabetes. The pharmacological intervention in signaling events that regulate the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and the catalytic subunit glucose-6-phosphatase (G-6-Pase) is regarded as a potential strategy for the treatment of metabolic aberrations associated with this disease. However, such intervention requires a detailed understanding of the molecular mechanisms involved in the regulation of this process. Glucagon and glucocorticoids are known to increase hepatic gluconeogenesis by inducing the expression of PEPCK and G-6-Pase. The coactivator protein PGC-1 has been identified as an important mediator of this regulation. In contrast, insulin is known to suppress both PEPCK and G-6-Pase gene expression by the activation of PI 3-kinase. However, PI 3-kinase-independent pathways can also lead to the inhibition of gluconeogenic enzymes. This review focuses on signaling mechanisms and nuclear events that transduce the regulation of gluconeogenic enzymes.
authors.affiliation: Department of Endocrinology, Heinrich-Heine-University Düsseldorf, D-40225 Düsseldorf, Germany. Andreas.Barthel@uni-duesseldorf.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Barthel
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmoll
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005809:Genes, Regulator / Q000502:physiology; D005943:Gluconeogenesis / Q000502:physiology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D009097:Multienzyme Complexes; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism*
chemical_list: D007328:Insulin; D009097:Multienzyme Complexes; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)