Tuesday, 21 August 2012

Exendin-4 activates glucokinase

Just a small note. Exendin-4 is a GLP-1 receptor agonist. Glucokinase is an enzyme that senses glucose levels, especially in the liver, where increased glucokinase levels reduce endogenous glucose production and increases glycogen synthesis.

People suffering from diabesity secrete significantly less GLP-1 in response to an oral carbohydrate load. Diabesity sufferers also have reduced glucokinase activity in the liver. See the link? ( 1, 2)

If you have Diabesity and eat 100g of glucose, you may only secrete enough GLP-1 for your liver to see ~50g of that glucose. What happens to the rest of the glucose that your liver doesnt see?

Well, since your liver cant see it, it cant do anything about it, the glucose may hit circulation where it causes the pancreas to secrete extra insulin ( hyperinsulinemia? ) Excessive glucose floating around in your blood that your liver doesnt know about cant be any good, glycation is serious business!

Remember also that glp-1 is a satiety hormone, it makes you eat less, and it also encourages fat oxidation over carbohydrate oxidation, I cant help but wonder now if this is exactly because GLP-1 activates glucokinase. Again peter was on the money with this post. If your liver is broke, through some combination of hepatic IR and reduced glp-1 secretion, you need to put down the carbs!

If you cant activate glucokinase to the correct amount of glucose you eat, then you cant do "paleo", lmao.

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