A bit late to reply, but my 2 cents is that is possibly could be the case. We know that obesity often happens in concert with insulin resistance. Theoretically, when one is in a chronic calorie surplus (gains weight), that would happen in concert with a lot of insulin secretion (either one is on a high-carbohydrate diet, or their high fat/protein diet would spare carbohydrates from oxidation, allowing for them to induce insulin secretion in the pancreas). A lot of insulin secretion would, in theory, lead to more of the insulin signaling cascade, would could theoretically lead to a lot of p70s6 kinase inhibiting IRS 1/2, serving as the "feedback mechanism" of the insulin signaling cascade, decreasing the "potency" of insulin's metabolic effects (such as clearing glucose from the bloodstream). I think the "potency" of insulin may possibly be inversely proportional to the activity of p70s6 kinase (which would make theoretical sense, since p70s6 kinase inhibits IRS 1/2), and I think it makes practical sense since weight loss (which would, in theory, lead to less insulin secretion) is generally prescribed to help with insulin resistance. Just my 2 cents, but hope this helps.
Saw an interesting video from Robert Lustig... is it possible that the liver's insulin receptors can be knocked out / resistant (and disrupt the FOXO pathway), yet *NOT* affect the SREBP-1c pathway?
PDK is not pyruvate dehydrogenase kinase ....it's phosphoinositide dependent protein kinase
Actually 3-phosphoinositide-dependent protein kinase 1
Thsnks, I waited this video for a long time.
Thank you sir
it was really confusing before
Thank you! So, P70S6K inhibiting IRS1/2 phosphorylation would have any relation to insulin resistance?
A bit late to reply, but my 2 cents is that is possibly could be the case.
We know that obesity often happens in concert with insulin resistance. Theoretically, when one is in a chronic calorie surplus (gains weight), that would happen in concert with a lot of insulin secretion (either one is on a high-carbohydrate diet, or their high fat/protein diet would spare carbohydrates from oxidation, allowing for them to induce insulin secretion in the pancreas). A lot of insulin secretion would, in theory, lead to more of the insulin signaling cascade, would could theoretically lead to a lot of p70s6 kinase inhibiting IRS 1/2, serving as the "feedback mechanism" of the insulin signaling cascade, decreasing the "potency" of insulin's metabolic effects (such as clearing glucose from the bloodstream).
I think the "potency" of insulin may possibly be inversely proportional to the activity of p70s6 kinase (which would make theoretical sense, since p70s6 kinase inhibits IRS 1/2), and I think it makes practical sense since weight loss (which would, in theory, lead to less insulin secretion) is generally prescribed to help with insulin resistance.
Just my 2 cents, but hope this helps.
thank you so much
Saw an interesting video from Robert Lustig... is it possible that the liver's insulin receptors can be knocked out / resistant (and disrupt the FOXO pathway), yet *NOT* affect the SREBP-1c pathway?
Hello sir . I need your help sir from where I can get the theory of these pathways
Yeah these things are really complicated 😅😅