Chapter 23 HORMONAL REGULATION AND INTEGRATION OF MAMMALIAN METABOLISM
- 23.1 Hormone Structure and Action
- 23.2 Tissue-Specific Metabolism
- 23.3 Hormonal Regulation of Fuel Metabolism
- 23.4 Obesity and the Regulation of Body Mass
- 23.5 Diabetes Mellitus
In Chapters 13 through 22 our focus has been on metabolism at the level of the individual cell, emphasizing central pathways common to almost all cells — bacterial, archaeal, and eukaryotic. We have seen how metabolic processes within cells are regulated at the level of individual enzyme reactions by substrate availability, by allosteric mechanisms, and by reversible covalent modification of enzymes.
To fully appreciate the significance of individual metabolic pathways and their regulation, we must view these pathways in the context of the whole organism. An essential characteristic of multicellular organisms is cell differentiation and division of labor. Specialized functions of the tissues and organs require specialized fuels and patterns of metabolism. Hormonal and neuronal signals integrate and coordinate the metabolic activities of different tissues and optimize the allocation of fuels and precursors to each organ. Although our focus is on mammalian systems, mammals are hardly unique in possessing hormonal signaling systems. Insects and nematode worms have highly developed systems for hormonal regulation, with fundamental mechanisms similar to those in mammals. Plants, too, use hormonal signals to coordinate the activities of their differentiated, specialized tissues.
In this chapter we will look at the specialized metabolism of several major organs and tissues and the integration of metabolism in mammals. We begin with an overview of the broad range of hormones and hormonal mechanisms, then turn to the tissue-specific functions regulated by these mechanisms. We discuss the distribution of nutrients to various organs, emphasizing the central role of the liver, and the metabolic cooperation among these organs. To illustrate the integrative role of hormones, we describe the interplay of insulin, glucagon, and epinephrine in coordinating fuel metabolism in muscle, liver, and adipose tissue. We also introduce other hormones, produced in adipose tissue, muscle, gut, and brain, that play key roles in coordinating metabolism and behavior. We discuss the long-term hormonal regulation of body mass and the role of obesity in the development of metabolic syndrome and type 2 diabetes. Finally, we discuss interventions used to manage diabetes.
In this chapter, we illustrate the following principles:
The tissues in a mammal are connected by a neurosecretory system that coordinates their activities. Mammals use chemically diverse hormones in a highly specific and multidirectional signaling system, connecting the tissues with each other and with the central nervous system.
Among the tissues and organs of an animal, there is a striking division of labor. The specialized role of each organ is reflected in its metabolic activities and capabilities. The circulatory system connects all of the tissues by carrying hormonal signals and metabolites between and among them.
Because the brain requires a continuous supply of glucose, maintaining an adequate concentration of glucose in the blood is a high priority in the activities of the other tissues. The liver integrates the use of fuels (glucose, fatty acids, and amino acids) by each tissue to keep the blood glucose level within the optimal range. Hormones carried in the blood (insulin, glucagon, epinephrine, cortisol) mediate this regulation.
Maintaining an optimal body mass is an important priority in the adult mammal. Body mass is a function of dietary intake, physical activity, and the choice of metabolic fuel, all of which are subject to hormonal regulation. Hormonal signals between the brain, the adipose tissue, and the gastrointestinal tract help to set activity and feeding behavior.
The metabolic activities of cells and organisms are complex and intertwined; perturbation at one point in the system has far-reaching consequences for health. When the normal energy-yielding metabolism of glucose and fatty acids is impeded by defective insulin signaling, the result is the disease diabetes.
The tissues in a mammal are connected by a neurosecretory system that coordinates their activities. Mammals use chemically diverse hormones in a highly specific and multidirectional signaling system, connecting the tissues with each other and with the central nervous system.
Among the tissues and organs of an animal, there is a striking division of labor. The specialized role of each organ is reflected in its metabolic activities and capabilities. The circulatory system connects all of the tissues by carrying hormonal signals and metabolites between and among them.
Because the brain requires a continuous supply of glucose, maintaining an adequate concentration of glucose in the blood is a high priority in the activities of the other tissues. The liver integrates the use of fuels (glucose, fatty acids, and amino acids) by each tissue to keep the blood glucose level within the optimal range. Hormones carried in the blood (insulin, glucagon, epinephrine, cortisol) mediate this regulation.
Maintaining an optimal body mass is an important priority in the adult mammal. Body mass is a function of dietary intake, physical activity, and the choice of metabolic fuel, all of which are subject to hormonal regulation. Hormonal signals between the brain, the adipose tissue, and the gastrointestinal tract help to set activity and feeding behavior.
The metabolic activities of cells and organisms are complex and intertwined; perturbation at one point in the system has far-reaching consequences for health. When the normal energy-yielding metabolism of glucose and fatty acids is impeded by defective insulin signaling, the result is the disease diabetes.