someone explain receptor to me like I have not read a paper in years
someone explain receptor to me like I have not read a paper in years. If this has been answered properly somewhere, link me and I will delete.
GIP receptor biology is genuinely unsettled — there is a live argument about agonism versus antagonism at the receptor — and the clinical results are robust regardless, which is an uncomfortable and interesting position.
Long half-life in this class comes from structural modification that promotes albumin binding and resists enzymatic degradation. Weekly dosing is a consequence of the molecule, not a convenience decision.
Glucose-dependent insulin secretion is why hypoglycaemia risk is low as monotherapy: the effect scales with glycaemia rather than acting unconditionally.
Research-use-only material is not approved for human use and nothing here should be read as a recommendation to use it.
best — the order this archive was captured in
Receptor expression in a tissue is necessary but not sufficient for an effect. You also need the agonist to reach it at relevant exposure, and that is where a lot of confident mechanism talk falls down.
Not convinced by the linearity assumption. Dose-response in this class is not linear and the trials show it.
Disagree. That is a preclinical finding in a rodent model and you are stating it as human pharmacology.
Speculation is welcome here if it is labelled. This one has been relabelled rather than removed.
Yes. The central component is the one that explains the reports on this site better than gastric emptying does.
Speculation is welcome here if it is labelled.
incretin_ivy is right that mechanism gives direction and not magnitude. Worth pinning.
dose response is not linear and nobody should assume it is
That conflates receptor affinity with clinical potency. They are related and they are not the same thing.
Tolerance to the gastric effect develops with continued exposure while the appetite effect largely persists. That single fact explains most of the "it settles but it still works" pattern the side-effect board reports.
Tolerance to the gastric effect develops with continued exposure while the appetite effect largely persists.
Agreed — and it is why the central and peripheral stories are complementary rather than rival.
That study was in a rodent model. Worth stating, since the thread has been reading it as human data.
Is there any human data on that mechanism yet?
Correction: that is glucose-dependent insulin secretion, which is why hypoglycaemia risk is low as monotherapy. Not the same claim as you made.
Read the primary paper after arguing about the summary for a fortnight. The discussion section said almost the opposite of what the thread had concluded.
gastric emptying slows, it does not stop
Agreed — the incretin effect is the load-bearing concept and everything downstream reads differently once you have it.
Agreed — the incretin effect is the load-bearing concept and everything downstream reads differently once you have it.
This is the concept everything else on this board is downstream of.
What was the exposure in that experiment relative to therapeutic?
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
Does the effect persist with continued dosing or does tolerance develop?
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
Small fix — it slows gastric emptying, it does not halt it, and the distinction matters for the mechanism you are proposing.
Yes. The discussion section is where the authors say what they actually think, and almost nobody here reads it.
Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped looking random.
receptor distribution is why the side effects are where they are
Same view. Tolerance developing to the gastric effect while the appetite effect persists explains most of what the side-effect board reports.
Correcting my own comment: I attributed that to the GIP arm and the paper attributes it to the GLP-1 arm.
What does the discussion section say about the limitation you are glossing?
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.
- 1Not convinced by the linearity assumption. Dose-response in this class is…6 comments in this branch · started by u/priya_guerrero