Chapter category: Endocrine

Hepatic Regulation of Fuel Metabolism

This chapter appears in the following book:

Mechanisms of Insulin Action

Edited by: Alan R. Saltiel and Jeffrey E. Pessin
ISBN: 978-0-387-72203-0
» Get more information about this book at landesbioscience.com «

Chapter authors:
Catherine Clark and Christopher B. Newgard

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It has been recognized for more than a century that the liver plays an important role in maintaining metabolic fuel homeostasis. The purpose of this chapter is to summarize mechanisms by which circulating glucose and lipid concentrations are controlled by hepatic metabolic activities. Glucose metabolism in the liver is under the tight control of the pancreatic hormones insulin and glucagon. A high insulin/glucagon ratio in the fed state favors pathways of glucose storage and disposal—glycogen synthesis, glycolysis, and the pentose monophosphate shunt—while a low insulin/glucagon ration in the fasted state favors the pathways of glucose production-glycogenolysis and gluconeogenesis. This tightly regulated control of hepatic glucose metabolism is disrupted in both major forms of diabetes, leading to inappropriate increases in glucose production by the liver. The quest to better understand the molecular and biochemical mechanisms of hepatic dysfunction in diabetes has resulted in the recent discoveries of new transcription factors, regulatory proteins, and allosteric factors, as well as new ideas about the role of spatial organization and compartmentalization in control of metabolic activity in the liver. Moreover, recent years have seen the emergence of new pathways of inter-organ communication in control of fuel homeostasis, with the liver as a central player. This chapter will therefore attempt to integrate these new findings with the bedrock of prior knowledge so as to provide a comprehensive summary of current knowledge of the role of liver in control of intermediary metabolism.

Catherine Clark

Christopher B. Newgard
Sarah W. Stedman Nutrition and Metabolism Center, Duke Independence Park Facility

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Chapter category: Endocrine

Hepatic Regulation of Fuel Metabolism

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