Central versus peripheral action: GLP-1 agonism works through both central nervous system effects (appetite) and peripheral effects (gastric motility, insulin). The balance is not fully characterised.
An honest declaration on GLP-1 receptor distribution: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.
Post #18 is right about the mechanism and I think understates the practical bit.
Ghrelin receptor agonism drives growth hormone release in pulses and also increases appetite, which is the effect people most reliably report and least often want.
Not the whole picture, but the part of it I can speak to.
Narrowing post #31, because the general version has more than one answer.
GLP-1 receptor signalling: the GLP-1 receptor is expressed on beta cells (insulin secretion), on neurons (appetite and gastric motility), and on myocardium (contractility). Different tissues respond to the same signal in different ways.
Glucagon receptor agonism raises energy expenditure and promotes hepatic fat oxidation. In a triple agonist the incretin limbs offset the glycaemic consequence, which is why the combination is not self-defeating.
Posting it because the silence on this was starting to look like agreement.
Nothing in receptor biology tells you what is in the vial, which is worth remembering when a mechanistic thread starts being used to justify a sourcing decision.
If this contradicts something upthread, the upthread version may well be the better one.
Post #71 put the caveat in the right place and I want to underline it.
The area postrema sits outside the blood-brain barrier and is where a great deal of the nausea signalling in this class originates. That is why the effect is central and not gastric irritation.
Read the full topic (99 posts)
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
Revisiting: GLP-1 receptor distribution: central and peripheral
Revisiting: GLP-1 receptor distribution: central and peripheral — setting out what I have, and where I think it stops being reliable. An honest uncertainty about GLP-1 receptor distribution rather than a…
|
+61 | 66 | 15k | 8mo |
|
Biased agonism: a real phenomenon, an over-used explanation — what changed since
Biased agonism: a real phenomenon, an over-used explanation — what changed since — setting out what I have, and where I think it stops being reliable. What changes if the standard account of Biased agonism is…
|
+49 | 56 | 47k | 17mo |
|
GIP receptor agonism and the argument about direction
GIP receptor agonism and the argument about direction — setting out what I have, and where I think it stops being reliable. A question about GIP receptor agonism that I think has a definite answer, unlike…
|
2 | 867 | 10mo | |
|
Follow-up: Glucagon receptor agonism in a weight-loss compound
Glucagon receptor agonism in a weight-loss compound Writing it up because I had to work it out twice and would rather nobody else did. A follow-up question about Glucagon receptor agonism that I did not know…
|
+5 | 9 | 21k | 7mo |
|
Biased agonism: a real phenomenon, an over-used explanation
Posting this under the heading it deserves: Biased agonism: a real phenomenon, an over-used explanation Everything below is what sits behind that. Trying to work out what would count as evidence on biased…
|
+130 | 135 | 23k | 16mo |
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
About the Tirzepatide category
Dual GIP/GLP-1 receptor agonist. SURPASS and SURMOUNT programme data, titration, and comparative discussion. This post is a community wiki: any member at trust level 3 or above can edit it, and every edit is…
|
+2 | 6 | 132 | 13mo |
|
Follow-up: Semaglutide versus liraglutide head to head: reading STEP 8 carefully
Semaglutide versus liraglutide head to head: reading STEP 8 carefully — setting out what I have, and where I think it stops being reliable. I would like to disagree carefully with the settled view on…
|
+1 | 5 | 11k | 20mo |
|
Tirzepatide molecular mass and the charge states you would expect on ESI — does this still hold?
Asking directly, because I could not find a straight answer: Tirzepatide molecular mass and the charge states you would expect on ESI — does this still hold? The question about Tirzepatide molecular mass that…
|
+7 | 11 | 281 | 6mo |
|
Tracking semaglutide's approved indications across jurisdictions, dated — does this still hold?
Tracking semaglutide's approved indications across jurisdictions, dated — does this still hold? — that is the question, and I have not found it answered plainly anywhere I have looked. Practical question…
|
+58 | 62 | 49k | 20mo |
|
Stepping down deliberately, and how to do it without losing progress
Stepping down deliberately, and how to do it without losing progress — setting out what I have, and where I think it stops being reliable. Practical question with the units stated, because I have seen how…
|
+98 | 102 | 26k | 3mo |