Gluconeogenesis: I keep hearing that it's only demand driven, can that be right?

(Bacon is a many-splendoured thing) #42

On the other hand, Dr. Bikman makes it sound that if you are already ketotic, you don’t need to worry about gluconeogenesis above the body’s actual need for it:


Though it’s always possible I misunderstood what he said.
(Diane) #43

I agree with your understanding though it’s always possible there is a difference for those eating ketogenically with high insulin resistance vs those who are sensitive to insulin.

(Jason Jodway) #44

Glucagon, cortisol, other catecholimines promote GNG. Insulin inhibits GNG. Leptin, T4, T3, Adiponectin influence the sensitivity to these signals not necessarily in a linear way. GH, IGF I’m sure play some part. There are potentially other unknown hormones, cytokines that have an effect. There are all sorts of signaling molecules we have little solid knowledge about so far.
FFA are relevant (somewhat speculative) because GNG is an energy consuming process so you have to have enough fuel for the liver plus extra and intrahepatic FA levels will reduce insulin action which is normally inhibitory of GNG.

Availability of amino acids is mostly to the extent that some are purely gluconeogenic, some are purely ketogenic, and some can be either, and that availability plus ratio drives the relative amount of glucose production versus ketone production. Less AA available means greater ketones, less glucose guaranteed.

As for how much is lost in urine, I’ve never seen any study data so I could only speculate. While typically elevated protein in urine makes one think of kidney failure, it is the typical trend that the more of something you consume in your diet, the more will be lost in urine as well. The reality is that the kidneys are not perfect and do lose useful nutrition over time.

(Doug) #45

Good explanation, Jason. It does get complex, but it’s fascinating in a “how this stuff works” way.

It would be insane for the body to not have gluconeogensis be at least almost all demand driven.

(mole person) #46

Right. So the fact that GNG is demand driven doesn’t ultimately change the fact that excess protein to needs will reduce ketogenesis. Some of those amino acids end up getting used in the Krebs cycle and so are contributing to ATP production thus reducing the need to turn to fat. Is that basically right?

You seem to know a great deal about this. Are you self taught or is this your field?