GLP-1 and the incretins explained
Every substance making the news around weight in recent years goes back to a discovery from the 1960s: your gut has a say in what your body does with a meal.
The puzzle of the sugar drip
In the 1960s researchers noticed something odd. Give someone sugar through a drip and a certain amount of insulin is released. Give the same amount of sugar by mouth and far more insulin is released. Even though blood sugar rose to the same level in both cases.
The explanation turned out to lie in the gut. As soon as food passes, cells in the gut wall release hormones that warn the pancreas in advance. Those hormones were named incretins. It is a forward-looking system: the body does not wait until the sugar is in the blood, it reacts at the front door.
Two incretins
| GLP-1 | GIP | |
|---|---|---|
| Where from | lower small intestine and colon | upper small intestine |
| Insulin | only when blood sugar is high | only when blood sugar is high |
| Stomach emptying | slows it | hardly any effect |
| Satiety | signals the brain | role less clear |
| Fat tissue | indirect | direct effects described |
An important detail in that table: both release insulin only when blood sugar is raised. At normal blood sugar nothing happens. That is a built-in brake which sets the whole system apart from insulin itself.
Why GLP-1 gets more attention
GLP-1 does more than drive insulin. It slows how fast the stomach empties, so a meal lingers. And it signals an area in the brainstem involved in fullness. Those three effects together explain why this hormone sits at the centre of weight research while GIP was long seen as a supporting act.
Natural GLP-1 is broken down within a minute or two by the enzyme DPP-4. For the body that makes sense: the signal belongs to this meal and should then go. It is also exactly the problem every copy has to solve.
How to make such a signal last
DPP-4 cuts GLP-1 at a fixed spot near the start of the chain. Every GLP-1 analogue is therefore modified at that point: it carries an amino acid the enzyme does not recognise. That takes you from two minutes to hours.
The second step is hanging a fatty acid tail on the chain. That tail clamps onto albumin, a protein swimming abundantly in the blood. While the peptide hangs there it is too big to be filtered out by the kidneys and it is shielded from enzymes. That takes you from hours to days.
Why GIP came back
For a long time GIP did not look interesting. That changed when substances acting on both receptors at once turned out to go further in research than those hitting GLP-1 alone. Exactly what GIP adds is still debated, but the fact that the combination does more than the sum is what gave the dual agonists their position.
That is also the point where this family started to branch. Read on in from single to triple agonist.
This site is made by the team behind Apex Bio Research, a Dutch supplier of research peptides with a certificate of analysis per batch.
Visit the shopThis site explains what the scientific literature says about peptides. It is not medical advice and not a set of instructions. The substances discussed here are research compounds: they are not approved for use in humans or animals. If you have a health question, see a doctor.
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