Fuel Metabolism by Insulin, Glucagon, and Other Hormones

• Glucose homeostasis is the maintenance of constant blood glucose levels.
• Insulin and glucagon are the two major hormones that regulate fuel mobilization and storage. They maintain blood glucose levels near 80 to 100 mg/dL despite varying carbohydrate intake during the day.
• If dietary intake of all fuels is in excess of immediate need, the excess fuel is stored as either glycogen or fat. Conversely, appropriate stored fuels are mobilized when demand requires.
• Insulin is released in response to carbohydrate ingestion and promotes glucose utilization as a fuel and glucose storage as fat and glycogen. Insulin secretion is regulated principally by blood glucose levels.
• Glucagon promotes glucose production via glycogenolysis (glycogen degradation) and gluconeogenesis (glucose synthesis from amino acids and other noncarbohydrate precursors).
• Glucagon release is regulated principally through suppression by glucose and by insulin. Glucagon levels decrease in response to a carbohydrate meal and increase during fasting. Increased levels of glucagon relative to insulin stimulate the release of fatty acids from adipose tissue.
• Glucagon acts by binding to a receptor on the cell surface, which stimulates the synthesis of the intracellular second messenger cAMP.
• cAMP activates protein kinase A, which phosphorylates key regulatory enzymes, activating some and inhibiting others.
• Insulin acts via a receptor tyrosine kinase and leads to the dephosphorylation of the key enzymes phosphorylated in response to glucagon.