genuine question about receptor that I am slightly embarrassed to ask
Slightly embarrassed to be asking this, but: genuine question about receptor that I am slightly embarrassed to ask.
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
The GIP question, which is the most interesting unsettled thing in this field.
Dual agonism at GIP and GLP-1 receptors produces clinical results that are robust and well replicated. What is not settled is the mechanism by which the GIP arm contributes — there is a genuine scientific argument about agonism versus antagonism at that receptor, with reasonable people and real data on both sides.
It is worth sitting with that. The clinical effect is not in doubt; the explanation is. That is an ordinary state of affairs in pharmacology and it is a good corrective to the confident mechanistic stories that circulate here.
Why mechanism talk keeps misleading people, including me.
A mechanism tells you a direction. It does not tell you a magnitude, a timescale, or whether the pathway is operative at the exposures involved. "Receptor X is expressed in tissue Y" is a fact; "therefore effect Z in a person" is a hypothesis with several missing steps.
The corrective is boring and it works: ask whether the evidence is preclinical or human, ask what exposure was used, and read the limitations section before the abstract. Most of the confidently wrong posts on this board — several of them mine — skipped all three.
Screenshot none of this. Read the whole thread, including the parts where I am told I am wrong.
best — the order this archive was captured in
Glucose-dependent insulin secretion is why hypoglycaemia risk is low as monotherapy: the effect scales with glycaemia rather than acting unconditionally.
Glucose-dependent insulin secretion is why hypoglycaemia risk is low as monotherapy: the effect scales with glycaemia rather than acting unconditional
Adding the caveat the paper itself makes in its limitations section, which is stronger than anything in this thread.
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
Speculation is welcome here if it is labelled. This one has been relabelled rather than removed.
incretin effect first, then everything else in this board makes sense
That study was in a rodent model. Worth stating, since the thread has been reading it as human data.
Disagree. That is a preclinical finding in a rodent model and you are stating it as human pharmacology.