[Question] gastric emptying — what am I missing here
gastric emptying — what am I missing here. I would rather ask a basic question now than get this wrong quietly for two months.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
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.
Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.
best — the order this archive was captured in
Speculation is welcome here if it is labelled. This one has been relabelled rather than removed.
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What was the exposure in that experiment relative to therapeutic?
glucagon agonism sounds paradoxical until you read the energy expenditure work
That conflates receptor affinity with clinical potency. They are related and they are not the same thing.
Agreed that receptor distribution is the key to the side-effect map. It is not a mystery, it is anatomy.
Disagree. That is a preclinical finding in a rodent model and you are stating it as human pharmacology.
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.
a mechanism you can state is not a mechanism you have demonstrated
tolerance to the gastric effect develops, appetite effect largely persists
mechanism explains a direction, not a magnitude
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
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.
- 1Speculation is welcome here if it is labelled. This one has been relabelled…7 comments in this branch · started by u/gastric_emptying_g