Integration of metabolism: fed, fasting and diabetes
Introduced| English | Meaning |
|---|---|
| fed state | fed state |
| fasting state | fasting state |
| glycated haemoglobin | glycated haemoglobin |
| diabetic ketoacidosis | diabetic ketoacidosis |
| insulin resistance | insulin resistance |
One system, one switch
- Metabolism is one system with a switch. Insulin and glucagon are the lever, the organs are the gears.
- Diabetes is the switch jammed, and the most useful single case in all of medicine for seeing how the parts fit.
Fed and fasting
- In the fed state 进食状态, insulin is high: glucose enters cells, glycogen fills, and extra carbon becomes fat.
- In the fasting state 空腹状态, glucagon is high: the liver breaks down glycogen (hours), then makes glucose (days), then makes ketones as the brain adapts.
Match each state to what the liver does.
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The liver is the arbiter; the hormone ratio and the time since eating decide which way it runs.
Worked example: the timeline of a fast
- 0–4 h: absorbed food is used and insulin falls. 4–12 h: liver glycogen drains. 12–24 h: the bank is nearly empty and gluconeogenesis ramps up from muscle amino acids, glycerol and lactate.
- Days 1–3: ketones rise and muscle protein is spared. By day 3 ketones give about a third of brain energy; after weeks, up to two-thirds.
Put the main glucose sources of a fast in the order they take over.
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Each source covers a time window, and each handover uses a mechanism from an earlier lesson.
How one signal sets every organ
- Glucagon raises cAMP, so PKA phosphorylates key enzymes (PFK-2, glycogen synthase, phosphorylase, fat lipase). Insulin lowers cAMP and switches on phosphatases, so the same enzymes lose their phosphates.
- One signal, read by four organs, keeps them from working against each other.
How does glucagon turn on glycogen breakdown in the liver?
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Glucagon → cAMP → PKA → phosphorylase on, glycogen synthase off. Insulin does the opposite, by removing those phosphates.
A three-month record
- Glucose sticks slowly to haemoglobin. Glycated haemoglobin 糖化血红蛋白 (HbA1c) builds up over the red cell's ~120-day life, so it records about three months of glucose.
- HbA1c ≥ 6.5% indicates diabetes. A glucose reading tells you about now; HbA1c tells you about the last three months.
Why does HbA1c reflect about three months of glucose?
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Glucose attaches slowly and permanently to Hb, so the fraction glycated records the average glucose over the cell's life.
The brain normally uses 120 g of glucose a day. On day 3 of a fast, ketones supply a third of its energy. How many grams of glucose a day does it still need?
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Two-thirds of 120 = 80 g, still supplied by gluconeogenesis, largely from muscle protein: which is why ketones that spare protein matter.
Worked example: the switch jammed off
- (Fictional patient, type 1 picture) With no insulin, cells read "fasting" even though blood glucose is high. Fat pours out, the liver floods the blood with ketones, and muscle breaks down.
- Ketones make the blood acidic, so breathing becomes deep and fast to blow off CO₂. Glucose spills into urine and drags water with it: thirst and dehydration. This is diabetic ketoacidosis 糖尿病酮症酸中毒.
In diabetic ketoacidosis, why does breathing become deep and fast?
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Ketone acids lower blood pH; breathing out more CO₂ partly corrects it. Every sign follows from one switch read as "fasting".
Type 2: the switch that sticks
- In type 2 diabetes insulin is present but tissues respond poorly: insulin resistance 胰岛素抵抗.
- The same ledger moves in the same direction, but more gently, over years instead of hours, and ketoacidosis is rare.
Three common slips
- "Insulin just lowers glucose." It sets the direction of every fuel: glucose, fat and protein.
- "The brain can skip glucose." Ketones replace only part of it, and only after days.
- Mixing HbA1c with glucose. HbA1c is a three-month average; a glucose reading is minutes.
Insulin's only job is to move glucose into cells.
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Insulin sets the direction of all fuels; without it fat breakdown and ketone production run unchecked, as in ketoacidosis.
Recap
- Insulin and glucagon are one lever on all organs: fed → store; fasting → glycogen, then new glucose, then ketones.
- Glucagon phosphorylates key enzymes through cAMP; insulin removes the phosphates.
- HbA1c ≥ 6.5% means diabetes; ketoacidosis is fasting metabolism running with high glucose.