Why are lactate level high in diabetes? For example, type II diabetes are resistant to insulin. If those patients are insulin resistant their gluconeogenesis should be working at a high rate and, because of that, lactate uptake by the liver should be removing lactate from the blood.

Alternatively, type I diabetics don't produce insulin, so the ratio insulin/glucagon would always be very low and gluconeogenesis should be stimulated... So I don't understand why lactate levels are high in diabetes... Can someone help me?

PS. This question came up after doing an experiment in school, with diabetic rats and normal rats. Diabetic rats had higher levels of lactate and my professor said that it was because the diabetic rats don't perform gluconeogenesis and so, lactate accumulates in the plasma. But it doesn't make sense for me.

  • $\begingroup$ I talked with my teacher and he said that one of the reasons that can contribute to this state of high lactate in diabetes is that diabetes patients are more likely to use aminoacids as gluconeogenic precursors than lactate, so lactate will accumulate in their blood. Hope this helps someone in the future. $\endgroup$
    – user5354
    Jan 11 '14 at 20:40

This condition is also known as "lactic acidosis" and can be pretty dangerous, since it influences the pH of the blood. When we metabolize glucose to produce ATP and NADH it is metabolized finally to pyruvate in a process called glyolysis (I am not going into detail here since this is nicely explained in the Wikipedia). Pyruvate can then be used further in the body in the Gluconeogenesis, the Citric acid cycle and other pathways. If a lot of energy is needed Pyruvate is converted by the pyruvate dehydrogenase into acetyl-CoA.

The problem with diabetes is that the pyruvate dehydrogenase can be inhibited in diabetes. If the body then needs a lot of energy pyruvate will be converted into lactate which is released by the cells into the bloodstream. Gluconeogenesis cannot be activated since this needs either Pyruvate, Acetyl-CoA or Oxaloacetate as starting material. The other problem with this process is that this happens in the liver and when the glucose is released into the bloodstream, it cannot be taken up by the cells due to the lack of insulin.

The conversion from Pyruvate to Lactate is katalysed by the Lactate dehydrogenase and needs NADH + H+ as a co-factor. The image below is from the Wikipedia article on Lactate dehydrogenase.

enter image description here

This reaction is highly exergonic which means its preferred direction is to the right side. To change this and make Pyruvate from Lactate you need an excess of NAD+ which usually only happens in the liver.

There is also an epidimiologic study available showing a strong correlation between elevated blood lactate levels and diabetes type II: "Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study."

  • $\begingroup$ Thanks, It was clear and explicit! But, one thing, can't you use that lactate to form piruvate by lactate desidrogenase and build a source of pyruvate to gluconeogenesis? Because if you think in the glucagon/insulin ratio (in type I) or insulin non-action in type II , the gluconeogenesis would be stimulated. $\endgroup$
    – user5354
    Jan 7 '14 at 20:16
  • $\begingroup$ Yes, and it dependends on the redox state of the cell, right? So if there's NAD+ sufficient, lactate should be converted to pyruvate... But okay, I'm beggining to understand why it can happen, although it's not clear for me the full mechanism. Thanks! :) $\endgroup$
    – user5354
    Jan 7 '14 at 20:36
  • $\begingroup$ Part1- What is not completly clear for me is how the accumulation is so noticeable since, by the way I was thinking, some gluconeogenesis is still ocurring. For example, in a normal person, insulin would bind to receptors and stimulate mTOR--> Akt --> akt would inhibit gluconeogenesis. But in Diabetes Type II, that mechanism would not occur because the receptors wouldn't sense insulin, so gluconeogenesis would actived. $\endgroup$
    – user5354
    Jan 7 '14 at 20:57
  • $\begingroup$ Part2-Now imagine that the rat is in the fasted state, it would be using fatty acids as fuel source, so there will be a lot of acetil-coA in the mitocondhria and NADH. If there's a lot of acetil-coA, piruvato desidrogenase would not be active, some glucose that would have been turned to piruvate would be converted to oxaloacetato by pyruvato carboxilase. So OAA and lactato could begin the gluconeogenic pathway... what am I thinking wrong? $\endgroup$
    – user5354
    Jan 7 '14 at 20:58
  • $\begingroup$ Yes, because Gluceoeogenesis uses energy to make glucose. The body on the other side needs energy badly (otherwise it wouldn't go for lactate. The production of lactate also consumes a lot of NADH (which is needed as you stated yourself in Gluconeogenesis) so it really doesn't make sense to build up (and use and conserve energy) and use it up at the same time. $\endgroup$
    – Chris
    Jan 7 '14 at 21:04

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