Four hormones dominate metabolic regulation: insulin, glucagon, epinephrine, and cortisol. Knowing what each does in each major tissue lets you reason through almost every MCAT metabolism passage.
Insulin
Secreted by pancreatic beta cells in response to high blood glucose (and incretins, amino acids). Signal: “store energy.”
Muscle / adipose: translocates GLUT4 to the cell surface, letting glucose enter; activates glycogen synthesis; activates lipoprotein lipase for fat storage.
Secreted by adrenal medulla in response to stress, exercise, low blood glucose. Signal: “fight or flight - mobilize everything fast.”
Similar to glucagon but faster, broader tissue distribution (including muscle).
Acts through beta-adrenergic receptors (Gs → cAMP → PKA) and some alpha receptors.
Activates glycogenolysis in liver AND muscle; activates lipolysis in adipose; increases heart rate and contractility.
Cortisol
Secreted by the adrenal cortex in response to chronic stress. Signal: “sustained mobilization + shift toward glucose conservation.”
Activates gluconeogenesis (liver) and proteolysis (muscle) - provides amino acids for glucose production.
Promotes lipolysis.
Immunosuppressive.
Slow-acting (steroid hormone, transcriptional effects over hours to days).
Who gives the orders: the fuel hormones
Regulation map
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Scroll sideways to see the whole map.
Hormone increases this process Hormone decreases it Little direct effect The enzyme each one acts through
Phosphorylated or notGlucagon and epinephrine both work through cAMP and PKA, so both end up phosphorylating the same enzymes. Insulin activates phosphatases, so it strips those phosphates off. This is why one rule covers most of metabolism: phosphorylation switches glycogen synthase off and glycogen phosphorylase on, and dephosphorylation does the reverse. Learn the rule once and you no longer have to memorize each enzyme.
Why cortisol looks slowCortisol is a steroid, so it crosses the membrane, binds a nuclear receptor, and changes transcription. Its effects take hours and work by changing how much enzyme exists rather than how active it is. That is why cortisol dominates prolonged fasting and chronic stress while epinephrine dominates the first minute of a sprint.
Epinephrine is tissue-specificIn the liver it drives glycogenolysis and the glucose leaves the cell, because the liver has glucose-6-phosphatase. In muscle the same signal drives glycogenolysis but the glucose-6-phosphate is trapped, so it can only be burned locally. Muscle glycogen never raises anyone else's blood sugar.
Four hormones, one grid. Insulin is the only one that says store; the other three all say release, for different reasons and on different timescales. Read a column to learn one hormone, read a row to answer the usual exam question, which is what happens to a single process when the hormonal state changes.
Muscle and adipose tissue lack glucagon receptors; only the liver expresses them. This is physiologically appropriate because only the liver has glucose-6-phosphatase and can release glucose into the blood. Muscle’s parallel mobilization of glycogen during stress is triggered by epinephrine, which does reach muscle via beta-adrenergic receptors.
How does insulin increase glucose uptake into muscle and adipose?
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Insulin binding to the receptor tyrosine kinase triggers a PI3K/AKT cascade that translocates GLUT4 transporters from intracellular vesicles to the plasma membrane. More GLUT4 at the surface means more glucose flowing into the cell down its concentration gradient. This mechanism is specific to muscle and adipose; the brain and liver use non-insulin-dependent GLUTs (GLUT1, GLUT2, GLUT3).
What is cortisol’s main metabolic effect during prolonged stress?
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Cortisol promotes proteolysis in muscle (to supply amino acids for gluconeogenesis) and gluconeogenesis in liver. It also stimulates lipolysis in adipose. The net effect is sustained mobilization of glucose and amino acids, with immune suppression as a side effect. Cortisol’s effects are slower than insulin and glucagon because it is a steroid hormone acting at the level of gene transcription (hours to days).
