AMPK and Type 2 Diabetes

I’ve written an article on a few supplements that have been shown to be helpful in raising and therefore normalizing AMPK levels in type 2 diabetics, and this did include a brief discussion of why this matters, but AMPK deserves an article of its own, as this is a pretty big deal when it comes to looking to manage T2, and if we don’t correct this imbalance, we’re just simply going to be in trouble.

For those of us who don’t mind highly technical reads, here’s a good scientific paper on the subject, although most people prefer these things explained in less technical language so that’s the purpose of this article.

So what’s AMPK anyway and why do we need to pay attention to this as type 2 diabetics?  AMPK plays a very important role in several processes, and a lack of it does have some very undesirable consequences, many of which are related to a lot of the things that happen to us with type 2, particularly the increased production of glucose in our livers that result from AMPK being too low.

This is at the heart of what is wrong with us, called excess gluconeogenesis, and the main reason why our blood sugar is too high with this disease, and this has even been shown to be the sole reason even, is that too much glucose is being put into our blood, mainly from our livers but also from our kidneys, and our intestines as well to a lesser degree, glucose that is supposed to only be reserved for times when our blood sugar needs to be raised to keep it stable.

What happens instead is that way too much of this is entering the system due to the regulatory mechanisms behind this being broken, it is not sensing things properly, and while insulin resistance, particularly in the alpha cells, plays a big role in this, low AMPK does as well and is well worth noting.

This extra glucose output relies on several sensors to activate it, for instance glucagon or cortisol, hormones that are designed to elevate our blood sugar in times of need, and excess glucagon is a huge deal with us, and too much cortisol will do the same thing, and a lot of us have excess cortisol as well.

The other major influencer here is low AMPK.  Glucagon rising is a sign of low blood sugar normally, cortisol is elevated in times where we require higher amounts of glucose in our blood, and low AMPK signals low cellular function which normally benefits from more glucose as well.

High insulin levels over time are behind the high glucagon through damage to the alpha cells of our pancreas, the higher inflammation that diabetes causes raises cortisol, and the insulin resistance that comes with all this ends up causing our AMPK levels to drop as well.

With insulin resistance, this changes our cellular metabolism where nutrients are restricted from entering cells, and this also tells the cell that it is deficient in nutrients, and this itself lowers AMPK levels at the cellular level.  This in turn causes our livers to release more glucose as it thinks we’re starving, and even though our cells may be getting plenty or even an excess of nutrients, the limiting factors of the insulin resistance does change AMPK expression and the body gets fooled by this so to speak.

So now, our blood sugar may already be high, but our livers continue to pump more glucose into our blood, as this low AMPK, as is the case with glucagon and cortisol as well, overrides our using blood sugar levels to decide this.  Whatever our blood sugar is, the low AMPK levels tell our liver that this isn’t enough, we need more glucose in our blood regardless, and this is exactly what happens.

AMPK activation also in itself increases glucose uptake, as when it is low, it limits this, so there is sort of a vicious cycle that develops here, glucose intake goes down, this lowers AMPK, which lowers glucose uptake, and so on.

Another effect of AMPK is that it limits excess insulin secretion by the beta cells of the pancreas, and excess insulin secretion is a hallmark of type 2 diabetes, and causes virtually every problem with not only type 2 diabetes but all metabolic diseases.

So this produces a vicious circle of an alarming magnitude, where insulin secretion is not curtailed, this leads to more insulin resistance, resulting in lower AMPK expression, which further increases insulin secretion, and so on.

The medical profession is so out to lunch on this that they don’t even realize excess insulin secretion is a problem, you have to actually go out and learn about diabetes to know this, and their only knowledge is what drug companies tell them basically, but this is all a very big deal and at the heart of the pathology of type 2 diabetes.

Excess free fatty acids also play a role here and they get out of hand more with low AMPK expression, and these are just some of the effects of low AMPK.  Not surprisingly, type 2 diabetics have low AMPK when we measure this in us.

Insulin resistance is of course a central feature of T2 diabetes and given that the lack of AMPK that we have plays a central role in worsening insulin resistance, through several pathways, AMPK activation is of great interest in treating type 2 diabetes.

We all know that physical exercise can benefit diabetes to some degree, and the main mechanism whereby this helps us has been shown to be the effects of exercise on increasing AMPK.

The number one anti diabetic drug, Metformin, works primarily by activating AMPK, so it’s not that there are no pharmaceutical drugs for this.  The class of meds known as TZD’s, Actos or Avandia for instance, does this as well but in a toxic and dangerous way.

Metformin is far more benign but has issues of its own, a number of different undesirable effects, which is why many have turned to natural medicines, particularly berberine, which has been shown to be as effective in increasing AMPK and therefore lowering blood sugar, without the side effects of Metformin, as well as offering several other additional benefits that are useful in not only managing type 2 diabetes but health in general.

There are other lesser known natural medicines that have been shown to be effective as well, gynostemma in particular, also known as jiaogulan or southern ginseng, which activates AMPK at least as well as berberine or metformin and perhaps even more effectively, although we haven’t really studied it all that much.  We really haven’t studied berberine anywhere near as much as we should have, but all indications are that both of these work as well as any prescription diabetic medication out there.

Quercetin, resveratrol, and alpha lipoic acid are three more common supplements that help increase AMPK, among other things, and the great thing about natural AMPK activators are that they can be stacked, you can take all of them together if you wish without worrying about toxicities like you do when you stack prescription meds.

I’m sure I’ll be talking about AMPK even more in future articles, as well as more specifics on how we can raise it back up, as this is a huge deal with type 2 diabetes.

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4 Comments on “AMPK and Type 2 Diabetes

    1. Well sadly enough no one has really studied this, although we really haven’t been able to control excess hepatic glucose with monotherapy, which leads us to believe that we haven’t been able to achieve ideal AMPK activation either. There’s more to these agents than just AMPK activation though, but if that’s all there was to it, you could just take more of something, berberine or gymnostemma for instance. That’s not a good idea with metformin of course because of its side effects, but we see better results with 3 grams a day with that and this dosage is often used in Europe. Now activating AMPK is going to affect protein synthesis, but I haven’t seen anything to suggest this is even a concern in humans, if you’re out for Mr. Universe this might be a concern, but on the other hand your diabetes should come first. There’s another side of this, this stuff prevents muscle atrophy from the diabetes itself, which messes up mitochondria quite a bit. The question isn’t whether berberine or other AMPK agents impair muscle synthesis, it’s by how much, and just saying it does isn’t even meaningful. I don’t think there’s any reason to believe that it does so in a way that would even be worth worrying about, let alone be considered as a reason not to use these agents for their anti diabetic benefits. It’s important to realize that this affect is directly a result of AMPK activation itself, although interestingly, this so called degradation is a result of the combination of increased AMPK accompanied by lower ATP, so the problem may be the lower ATP itself, so in other words we need to improve mitochondrial function to address this which is something that type 2 diabetics tend to have a real issue with. So this involves looking at adding things such as PQQ and CoQ10 among other things to help offset this, to address the real problem, low cellular metabolism. There’s also the effect that AMPK has on insulin production, and insulin is very anabolic, so reducing that from the excessively high levels, as we must for the sake of our metabolism and disease, may in itself be catabolic, but this is something that is necessary. It’s always about seeking net benefits and given the cascade of negative effects of low AMPK I can’t imagine what looks like a pretty meaningless downregulation of muscle synthesis offsetting the benefits of these agents, even stacking them, and if raising AMPK does that then so be it. Good question though!

  1. Thanks for the reply. If you do stack AMPK activators or take a high dose of a single compound, how do you choose specific doses for them? If there is little hypoglycemia, why not just take the max dose?

    1. Generally people use the dosages on the bottle or if they are diabetic, the ones used in studies. 1000-2000 mg of berberine, 450 to 3 grams of gynostemma. These are herbal supplements so taking them both together wouldn’t be something we would normally worry about. If someone is using these as an anti diabetic they can decide whether taking both yields enough of an additional benefit. There is no max dose here, and we haven’t even studied higher ones, but one could try that and see how it goes I if one wanted to I guess.

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