In human studies involving an overnight fast (24 hours) followed by refeeding, researchers used SOMAScan technology to analyze serum protein changes. MFGE8 was among the proteins that increased upon refeeding and was elevated compared to the fasting state PubMed.
Summary Table
| Metabolic State | MFGE8 Levels |
|---|---|
| Fasting (5–16 h) | Decreased |
| Refeeding (After Fast) | Increased |
Reducing insulin sensitivity after refeeding seems paradoxical at first, but it makes sense when you consider the physiological priorities of a mammal that just transitioned from fasting to feeding:
1. Preventing hypoglycemia after a large nutrient influx
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After refeeding, blood glucose spikes. If insulin sensitivity were maximized everywhere (muscle, adipose, liver), glucose would be cleared from the blood too quickly.
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That could risk a sudden dip (reactive hypoglycemia), leaving the brain under-fueled.
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By slightly dampening insulin sensitivity, peripheral tissues don’t “over-suck” glucose out of circulation, keeping a steady supply for the brain and red blood cells.
2. Prioritizing safe storage over rapid uptake
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Insulin resistance is not a binary state — it can be tissue-specific and context-dependent.
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After refeeding, reducing insulin sensitivity in muscle may favor directing glucose toward liver glycogen storage and lipid synthesis in adipose tissue rather than immediate burning in muscle.
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This helps rebuild energy reserves for the next fasting period.
3. Supporting immune cell function
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Postprandial periods are often when the gut immune system is most active (monitoring incoming antigens, microbes).
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Immune cells rely heavily on glucose. A slight reduction in muscle/adipose glucose uptake ensures immune cells have access to fuel.
4. Evolutionary “thrifty” strategy
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Wild mammals did not eat 3–5 regular meals per day; feeding was intermittent and unpredictable.
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A mechanism that slows down glucose disposal after feeding would help stretch nutrient availability between meals and stabilize energy supply.
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From this angle, MFGE8’s rise upon refeeding could be part of an energy allocation program: allow some storage, avoid overshoot, and keep circulation glucose levels safe for the brain/immune system.
✅ In short:
Reducing insulin sensitivity after refeeding helps avoid dangerous glucose crashes, ensures brain and immune access to glucose, and promotes balanced storage rather than immediate overconsumption by muscle/fat.
Hypoglycemia, despite the appearance of being good for you, sets you up for heart attack and stroke. How? The following is how:
Effect of Hypoglycemia on Inflammatory Responses and the Response to Low-Dose Endotoxemia in Humans
It causes a storm to erupt in the blood stream, that which is very conducive to plaque rupture, plaque destabilization, and thrombosis.
