Chapter 41: Actions of Hormones that Regulate Fuel Metabolism

Insulin functions as the primary anabolic hormone, promoting storage of carbohydrates as glycogen, synthesis and storage of triacylglycerols in adipose tissue, protein synthesis in muscle, and simultaneous suppression of fuel mobilization during the fed state. Amylin works synergistically with insulin by delaying gastric emptying, reducing appetite, and maintaining favorable insulin-to-glucagon ratios that optimize metabolic storage. In contrast, glucagon serves as the major counterregulatory hormone during fasting, activating glycogenolysis and gluconeogenesis in the liver to sustain blood glucose levels and stimulating ketogenesis to provide alternative fuel sources. The catecholamines, including epinephrine and norepinephrine, oppose insulin's actions by increasing lipolysis, glycogenolysis, and gluconeogenesis while simultaneously reducing insulin secretion. Cortisol contributes to stress responses by mobilizing amino acids from muscle, enhancing hepatic gluconeogenesis, and promoting central fat redistribution. Somatostatin acts as a broad inhibitory hormone, suppressing secretion of multiple hormones and reducing nutrient absorption, with synthetic analogs like octreotide used therapeutically in conditions such as acromegaly. Growth hormone exhibits complex metabolic effects, promoting muscle protein synthesis and nitrogen retention while simultaneously increasing lipolysis and impairing glucose uptake in peripheral tissues, thereby exerting a diabetogenic effect. Thyroid hormone increases overall metabolic rate through enhanced oxidative metabolism, stimulates glycolysis and lipolysis, and increases heat production or calorigenesis. Gastrointestinal-derived incretins, particularly glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, enhance insulin secretion in response to nutrient intake and have become important therapeutic targets in type 2 diabetes management through agonist and inhibitor approaches. The autonomic nervous system further modulates metabolism through vagal stimulation of insulin secretion and sympathetic inhibition during stress responses. Clinical applications include recognition of acromegaly and Cushing syndrome resulting from excessive hormone production, emphasizing how dysregulation of these pathways leads to metabolic disease.