Pancreatic signals controlling food intake; insulin, glucagon and amylin

Abstract

The control of food intake and body weight by the brain relies upon the detection and integration of signals reflecting energy stores and fluxes, and their interaction with many different inputs related to food palatability and gastrointestinal handling as well as social, emotional, circadian, habitual and other situational factors. This review focuses upon the role of hormones secreted by the endocrine pancreas: hormones, which individually and collectively influence food intake, with an emphasis upon insulin, glucagon and amylin. Insulin and amylin are co-secreted by B-cells and provide a signal that reflects both circulating energy in the form of glucose and stored energy in the form of visceral adipose tissue. Insulin acts directly at the liver to suppress the synthesis and secretion of glucose, and some plasma insulin is transported into the brain and especially the mediobasal hypothalamus where it elicits a net catabolic response, particularly reduced food intake and loss of body weight. Amylin reduces meal size by stimulating neurons in the hindbrain, and there is evidence that amylin additionally functions as an adiposity signal controlling body weight as well as meal size. Glucagon is secreted from A-cells and increases glucose secretion from the liver. Glucagon acts in the liver to reduce meal size, the signal being relayed to the brain via the vagus nerves. To summarize, hormones of the endocrine pancreas are collectively at the crossroads of many aspects of energy homeostasis. Glucagon and amylin act in the short term to reduce meal size, and insulin sensitizes the brain to short-term meal-generated satiety signals; and insulin and perhaps amylin as well act over longer intervals to modulate the amount of fat maintained and defended by the brain. Hormones of the endocrine pancreas interact with receptors at many points along the gut-brain axis, from the liver to the sensory vagus nerve to the hindbrain to the hypothalamus; and their signals are conveyed both neurally and humorally. Finally, their actions include gastrointestinal and metabolic as well as behavioural effects.

Figure 1

Insulin is secreted into the blood from the pancreas in direct proportion to the amount of fat stored in white adipose tissue. As it circulates through brain capillaries, a small amount of insulin is transported into the brain where it acts on insulin receptors on neurons with either net catabolic or anabolic activity, for example in the arcuate nucleus of the hypothalamus. These neurons in turn influence energy homeostasis (food intake and energy expenditure) and ultimately the amount of fat stored in the body by exerting a net catabolic action.

Figure 2

Insulin, glucagon and amylin are all secreted from the endocrine pancreas, and all participate in the regulation of energy homeostasis. Insulin acts at both the liver and the forebrain to reduce energy intake as well as to suppress hepatic glucose production. Glucagon acts mainly at the liver where it increases glucose production while generating a signal to reduce energy intake that is relayed to the hindbrain. Amylin acts directly at the hindbrain to reduce energy intake. NTS, nucleus of the solitary tract; AP, area postrema; + indicates stimulation.