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089: Why AGEs and deficient insulin signaling are the main problem in diabetes.

Masterjohn Q&A Files Episode 89


The reason that methylglyoxal, which I did my doctoral dissertation on, the reason that methylglyoxal, which is quantitatively the most important form of advanced glycation end products in diabetics, the reason that it is elevated is not because of hyperglycemia. It's because of deficient insulin signaling.

That is for two reasons. One is that you can derive methylglyoxal from glycolysis. You can derive methylglyoxal from ketogenesis. You can derive methylglyoxal from protein, specifically from the amino acid threonine. Insulin prevents you from making methylglyoxal in the glycolytic pathway no matter how high the glucose level is. Insulin, what it does in glycolysis is at the step where the intermediates spill out to generate methylglyoxal, insulin stimulates that enzyme that sucks the intermediates down.

The role of methylglyoxal starts at the first instance of hyperglycemia to cause the development from an acute first ever instance of hyperglycemia through the pathway of developing diabetes. Then in diabetes, methylglyoxal is overwhelmingly responsible for causing the cardiovascular complications, the complications in the eyes, and the neurological complications of diabetes, cataracts, all of these things. And so I think it's a huge mistake to think that the spiking glucose is the thing going on rather than the deficient insulin signaling.

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The Masterjohn Q&A Files
We use Zoom, a video chatting software, in webinar mode. You can ask your question anonymously in text, but you can also ask it publicly, and you can even get "on stage" and share your mic, web cam, or screen with everyone.
Chris Masterjohn, PhD