Carbohydrate metabolism and the liver: actual aspects from physiology and disease.
The liver plays a unique role in controlling carbohydrate metabolism by maintaining glucose concentrations in a normal range. This is achieved by a tightly regulated system of enzymes and kinases regulating either glucose breakdown or synthesis in hepatocytes. This process is under the control of glucoregulatory mediators among which insulin plays a key role. In type 2 diabetes, as well as in liver disease, alterations in hepatic glucose metabolism like an increased post-absorptive glucose production together with diminished glucose uptake following carbohydrate ingestion occur, implying insulin resistance as a central pathological principle. Knowledge of the processes involved in maintaining glucose homeostasis as well as insulin resistance is a prerequisite to develop new therapeutic approaches in diabetes as well as in liver disease. In the recent years, genetically-altered mouse models that have helped to identify enzymes, transcription factors and mediators that are essential for maintaining glucose homeostasis in the liver and provide a valuable tool to study carbohydrate metabolism in liver disease. In this current review, genetically manipulated animals either overexpressing or lacking key gluconeogenic enzymes, hepatic transcription factors, IGF-1, hepatic insulin receptors, adipokines and hepatitis C core antigen will be discussed in the context of human disease.
Raddatz
D
D
Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August-University, Göttingen, Germany. draddat@gwdg.de
Ramadori
G
G
D000818:Animals; D050260:Carbohydrate Metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008954:Models, Biological
D004040:Dietary Carbohydrates; D005947:Glucose