title: [Glyceroneogenesis and PEPCK-C: pharmacological targets in type 2 diabetes].
abstract: Obesity is a major risk factor for insulin resistance and type 2 diabetes. The link between hypertrophied adipose tissue and this pathology is thought to be non-esterified fatty acids (NEFA) arising from adipocyte lipolysis. Sustained increase in plasma NEFA induces insulin resistance. In adipocytes, a significant part of lipolytic NEFA is re-esterified to triacylglycerol. Re-esterification requires glycerol-3-phosphate which, during fasting, is synthesized from lactate, pyruvate or certain amino acids in a metabolic pathway named glyceroneogenesis. The key enzyme in this pathway is the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C). In this review, we postulate that thiazolidinediones exert their hypolipidemic and antidiabetic effects in adipose tissue at least in part through a rapid and selective induction of PEPCK-C gene transcription leading to increased PEPCK-C and glyceroneogenesis. Subsequent fatty acid re-esterification participates in the reduction in blood NEFA and insulin resistance.
authors.affiliation: Inserm UMR-S 747 ; Université Paris Descartes, Centre universitaire des Saints-Pères, 45, rue des Saints-Pères, 75006 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cadoudal
authors.forename: Françoise
authors.initials: F
authors.lastname: Fouque
authors.forename: Chantal
authors.initials: C
authors.lastname: Benelli
authors.forename: Claude
authors.initials: C
authors.lastname: Forest
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D008055:Lipids / Q000502:physiology; D009765:Obesity / Q000503:physiopathology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005990:Glycerol