Fed and fasting states

Insulin moves GLUT4 carriers from vesicles to the plasma membrane, so glucose enters muscle and fat cells by facilitated diffusion.

• Correct: Moves GLUT4 glucose carriers into their plasma membranes:
• Makes them release glucose into the blood:
• Blocks their uptake of amino acids:

Ketogenesis turns excess acetyl CoA into ketone bodies. Acetyl CoA cannot be turned into glucose or glycogen.

• Glucose:
• Correct: Ketone bodies:
• Glycogen:

Cortisol breaks down muscle protein and switches on gluconeogenesis in the liver, which turns the released amino acids into glucose.

• Builds it up:
• Has no effect on it:
• Correct: Breaks it down, releasing amino acids:

In the absorptive state, insulin is high and glucagon low. The liver takes up glucose, switches on glycogenesis, and switches off glycogenolysis. It stops releasing glucose into the blood; the little gluconeogenesis that continues feeds glycogen.

• Releasing glucose from its glycogen: Glycogenolysis is switched off after a meal; the liver is storing glucose, not releasing it.
• Making glucose from amino acids: Insulin stops the liver releasing new glucose into the blood; any glucose it still makes goes into glycogen.
• Correct: Taking it up and storing it as glycogen: Correct. The fed liver stores glucose as glycogen.
• Turning it into ketone bodies: Ketogenesis runs when insulin is low and fat breakdown is fast, not after a carbohydrate meal.

A week without food drives insulin down and lipolysis up across the endocrine system and adipose tissue. The liver's glycogen is gone, and it makes ketone bodies from fatty acids. The brain, the nervous system's heaviest glucose user, switches partly to ketone bodies, lowering its glucose need and sparing muscle protein.

• Insulin in the blood: down. Without food, glucose stays at the low end of normal and beta cells release little insulin.
• Lipolysis in adipose tissue: up. Low insulin removes the brake on lipolysis, and growth hormone, cortisol and sympathetic activity push it further.
• Ketone bodies in the blood: up. The liver turns the flood of fatty acids into ketone bodies, whose level climbs over the first week.
• Liver glycogen: down. Liver glycogen is used up within about a day; after a week almost none is left.
• Glucose used by the brain each day: down. The brain takes up ketone bodies in proportion to their level, so it needs less glucose.

Early in a fast, most new glucose is made from amino acids. As ketone bodies rise, the brain takes more of its energy from them, so less glucose, and therefore less protein, is needed.

• Correct: The brain needs less glucose as ketone bodies rise: Correct. The two panels move together: more ketone use, less protein broken down.
• The muscles have run out of protein: Most muscle protein is still there at day 28; breakdown falls because less is needed.
• Insulin rises and blocks protein breakdown: Insulin stays low throughout a fast; that is what keeps lipolysis and ketogenesis high.
• The liver switches to making glucose from fatty acids: Fatty acids cannot be made into glucose; they are made into ketone bodies instead.

Glucose between meals comes only from the liver's glycogen and gluconeogenesis. When muscle and most other tissues burn fat instead, that glucose is left for the brain and red blood cells, which depend on it. This is glucose sparing.

• It lets muscle release its stored glycogen as glucose for the other tissues: Muscle keeps its glycogen for itself; it cannot release glucose into the blood.
• Correct: It keeps the limited glucose supply for the brain and red blood cells: Correct. Glucose sparing protects the brain's supply.
• It raises insulin release from the pancreas: Insulin is low between meals, and burning fat does not raise it.
• It lets the liver turn fatty acids into glucose: Fatty acids cannot be made into glucose.

Without insulin, the signal of plenty is missing. His liver keeps releasing glucose, muscle and fat take little up, lipolysis runs unchecked and the liver makes ketone bodies. His body acts as if it were fasting, even with glucose far above normal.

• Correct: A fasting pattern: releasing glucose and burning fat: Correct. Hormonally, he is in an extreme fasting state.
• The absorptive state: storing the extra glucose as glycogen and fat: Storage in the absorptive state depends on insulin, which he lacks.
• Normal between-meal balance, with glucagon matching the glucose level: With no insulin, glucagon is not restrained, and the liver keeps adding glucose to already high blood levels.
• The absorptive state in the liver, with fasting only in muscle: Without insulin, the liver also releases glucose rather than storing it.

After a carbohydrate meal, glucagon release falls. Rising glucose and insulin damp the alpha cells. High insulin with low glucagon is what defines the absorptive state.

• Glucose and amino acids reach the liver through the hepatic portal vein: This step is right. The portal vein carries absorbed glucose and amino acids to the liver first.
• Beta cells release insulin as glucose rises: This step is right. Rising glucose drives insulin release.
• Correct: Alpha cells raise glucagon release to match: This is the error. Glucagon falls after a carbohydrate meal.
• Muscle moves GLUT4 into its membrane and stores glycogen: This step is right. Insulin moves GLUT4 to the membrane, and muscle stores glycogen.
• Adipose tissue stores triglyceride and switches off lipolysis: This step is right. Insulin drives fat storage and blocks lipolysis.

Growth hormone is catabolic for fat, driving lipolysis so that tissues burn fat, and anabolic for protein, through IGF-1, which limits muscle breakdown. It also opposes insulin's effect on glucose, helping keep blood glucose up.

• It builds glycogen stores and lowers blood glucose: Growth hormone raises blood glucose rather than lowering it.
• It raises insulin release and stores fat: Growth hormone opposes insulin and releases fat rather than storing it.
• It blocks ketogenesis and raises glucose use: By releasing fatty acids, growth hormone supports ketogenesis, and it reduces glucose use.
• Correct: It releases fat for fuel but limits protein loss: Correct. Fat out, protein kept: both help during a fast.