[Meta] proposal — a flair for receptor posts
proposal — a flair for receptor posts, and it will stay as it is unless somebody makes the case to change it.
The mental model, in four steps, that makes the rest of this site legible.
One: gut hormones amplify the insulin response to food. Two: agonists at those receptors act peripherally on insulin secretion and gastric emptying, and centrally on appetite. Three: structural modification gives them a long half-life, so exposure is smooth and weekly. Four: tolerance develops to some effects and not to others.
From those four, most of what the experience boards report falls out: why the side effects cluster early, why they settle at a stable dose, why appetite reduction persists, and why the scale and the appetite move on different clocks.
Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
That is everything I have. The rest is opinion and I have tried to keep it out.
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.
Are we talking about receptor affinity or clinical potency?
glucagon agonism sounds paradoxical until you read the energy expenditure work
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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.
Cosigning on GIP. The genuinely interesting thing is that the biology is not settled and the clinical result is nonetheless robust.
Retitled to distinguish preclinical from clinical, which the original ran together.
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.
- 1Receptor expression in a tissue is necessary but not sufficient for an…6 comments in this branch · started by u/santiago_rasmussen