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Fed vs Fasted State: Insulin, Glucagon and Metabolic Switches
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After a meal, insulin dominates and the body stores fuel. During fasting, glucagon (with epinephrine and cortisol) dominates and the body releases it.
Hormone comparison
| Insulin (fed) | Glucagon (fasting) | |
|---|---|---|
| Source | Pancreatic beta cells | Pancreatic alpha cells |
| Blood glucose | Lowers | Raises |
| Liver glycogen | Synthesis (glycogen synthase) | Breakdown (glycogen phosphorylase) |
| Liver glucose | Glycolysis, fatty acid synthesis | Gluconeogenesis |
| Adipose | Stores triglycerides (lipoprotein lipase) | Lipolysis (hormone-sensitive lipase) |
| Signaling | Receptor tyrosine kinase | G protein, cAMP, PKA |
Insulin promotes dephosphorylation of key enzymes (active glycogen synthase). Glucagon promotes phosphorylation (active glycogen phosphorylase).
Time course of fasting
| Stage | Glucose source | Main fuel for other tissues |
|---|---|---|
| Fed (0 to 4 h) | Diet | Glucose |
| Early fasting (4 to 16 h) | Liver glycogenolysis | Glucose; fatty acids in muscle |
| Fasting (about 1 to 3 days) | Gluconeogenesis (lactate, glycerol, amino acids) | Fatty acids; brain still uses glucose |
| Prolonged starvation | Gluconeogenesis, less protein breakdown | Ketone bodies used by brain |
Organ roles
- Liver: the glucose supplier; the only organ that releases free glucose (it has glucose-6-phosphatase) besides kidney.
- Muscle: keeps its own glycogen; lacks glucose-6-phosphatase, so it cannot export glucose. Releases lactate and alanine.
- Adipose: releases fatty acids and glycerol.
- Brain: glucose first, ketones in long fasts. It cannot use fatty acids directly.
- Red blood cells: always glucose (no mitochondria).
Common traps
- Letting muscle glycogen raise blood glucose. It cannot.
- Saying the brain burns fatty acids. It uses ketones.
- Mixing up the cell types. Beta makes insulin; alpha makes glucagon.
One-minute recap
- Fed: insulin, store. Fasted: glucagon, release.
- Glycogen first, then gluconeogenesis, then ketones.
- Only liver (and kidney) export glucose.
Check yourself: 5-question mini-quiz
1. Which hormone activates glycogen phosphorylase in the liver?
Glucagon, through cAMP and PKA.
2. Which tissue cannot release glucose from glycogen into blood?
Muscle, which lacks glucose-6-phosphatase.
3. What is the main glucose source in the first hours of fasting?
Liver glycogenolysis.
4. What fuel does the brain use in prolonged starvation?
Ketone bodies, along with some glucose.
5. Which cells secrete insulin?
Pancreatic beta cells.
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