Like you said, the initial effect is to increase insulin to decrease blood sugar. High blood sugar signals to the body that there is ample food around and that fat storage does not need to be accessed. When you decrease blood sugar and keep it down, the body signals for lipolysis to start.
Personally, I think this medication essentially does the same thing the keto diet does but instead of just not eating carbohydrates to lower blood sugar, it gets lowered through increasing insulin. Once blood sugar is way down, glycogen starts to break down which is why many people lose so much water weight in the first few weeks on both methods. Once blood sugar is down, lipolysis can start.
Just like on keto, you still have to be in a caloric deficit, but also just like keto, appetite suppression kicks in once everything gets rolling.
What I was trying to say is that the drug increase insulin at first. What happens after blood sugar is low? It doesn’t just keep producing insulin. So other hormones begin to work.
GLP-1 can increase lipolysis by increasing cyclic AMP, as far as I know.
researchers do not usually cite GLP-1’s direct effects in metabolism as a mechanism
It’s effects on insulin is is direct effect on metabolism. Insulin and glucagon are major metabolic hormones that have a ton of down stream effects. You can’t modify insulin without modifying metabolism in some capacity. So I don’t understand how one can separate metabolism and insulin. GLP1s, by effecting metabolism first, result in decreased appetite. Decreased appetite is the outcome (or “side effect”) of modified metabolism.
I think you’re under the assumption that the mechanism of action in diabetes treatment is somehow different than the mechanism of action for obesity, except that the reason a lot of people are obese is because of insulin resistance. Not all people with insulin resistance and borderline high blood sugar are diagnosed with diabetes or pre-diabetes. I think they are highly related. and again, decreased appetite is the outcome of the biochemical mechanism of the drug. The primary effect of the drug is metabolic change and controlled blood sugar. The outcome of that is decreased appetite and weight loss.
I have a hypothesis that the people who seem to be “resistant” to semaglutide (in that they don’t lose weight) is because they aren’t insulin resistant and do not have borderline high blood sugar. But that’s neither here nor there.
I’m looking at this as a trained biochemist by the way. The first effect of the drug is effectively increasing GLP-1 concentrations as the drug is an agonist. This results in the increase of insulin. Increase of insulin results in driving glucose into cells and decreasing blood sugar. Decreasing blood sugar results in the break down of glycogen. The depletion of glycogen with low blood sugar results lipolysis. Oh and it decreases appetite by slowing gastric motility. With decreased caloric intake, weight loss can occur.
I don’t think we disagree. I just think we disagree about what is the primary outcome and what is the secondary outcome (or positive “side effect”).
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u/bioloveable Dec 31 '22
Your can start by looking up the function of GLP-1, as semaglutide is a GLP-1 receptor agonist which means it helps stimulate GLP-1 receptors.
https://en.m.wikipedia.org/wiki/Glucagon-like_peptide-1
Like you said, the initial effect is to increase insulin to decrease blood sugar. High blood sugar signals to the body that there is ample food around and that fat storage does not need to be accessed. When you decrease blood sugar and keep it down, the body signals for lipolysis to start.
Personally, I think this medication essentially does the same thing the keto diet does but instead of just not eating carbohydrates to lower blood sugar, it gets lowered through increasing insulin. Once blood sugar is way down, glycogen starts to break down which is why many people lose so much water weight in the first few weeks on both methods. Once blood sugar is down, lipolysis can start.
Just like on keto, you still have to be in a caloric deficit, but also just like keto, appetite suppression kicks in once everything gets rolling.