Metformin is a Miracle Drug: A Picture is Worth 10,000 Words!

Don’t be spooked by this picture! You may not have a science background, but many of us face the challenge of being overweight or having type 2 diabetes. If you have these problems, it is essential that you understand your disease enough to achieve the maximum possible protection from complications like amputation or heart attack and this picture is worth 10,000 words. I have previously written about the master metabolic genetic switch AMPK. In this slide, AMPK is in the center. The red and green lines represent genes that AMPK regulates. A red line means AMPK down regulates the gene. A green line means that AMPK up regulates the gene. This is just a small sample of the numerous genes that AMPK can influence.

AMPK influences genes involved in a wide array of metabolic pathways, including glucose and fat metabolism, nutrient uptake, oxidation, molecular synthesis, and forming new mitochondria. AMPK is also involved in identifying and recycling worn out cell parts. AMPK maintains cells. AMPK reduces the effects of inflammation and stress. AMPK influences the expression of a substantial number of genes, likely in the dozens to hundreds, depending on the specific cellular and environmental conditions. The impact of AMPK on gene expression is a dynamic and intricate process involving multiple layers of regulation. It is hard to overstate the importance of AMPK activation on reducing your likelihood of having diabetic complications or trouble from related conditions.

This network of hundreds of genes regulated by AMPK evolved for one purpose and that is to help the fetus and child survive when there is no food. It retains that function throughout life. That is why reduced calorie diet and fasting are are associated with longer, healthier lives. As you can see from the diagram, it is not just NAD+, SIRT1, or FOXO that promotes are a longer healthier life, it is all of those factors integrated and regulated by AMPK.

Now we can get back to how this all relates to metformin and ADMA. Severe starvation switches on AMPK and switches off mTOR via the same exact nutrient sensing mechanism. The amino acids that make up proteins are well known to activate this nutrient sensing mechanism and ADMA is structurally very much like the amino acid arginine. ADMA is elevated in obesity in obesity and type 2 diabetes. ADMA activates this nutrient sensing mechanism to enhance mTOR activity and diminish AMPK activity. Metformin precisely blocks that effect to produce a state that mimics starvation or fasting to reduce complication rates in type 2 diabetes. Metformin directly enhances the activity of AMPK the survival switch and that is why it is a precision medicine— a wonder drug— that directly blocks the root cause of many diabetic complications while supporting a longer, healthier life. Proof exists that a protocol containing metformin extends healthier life in diabetes by 8 years.

Understanding this science is not that hard and it is so important for your health. It is like learning to say “where is the bathroom in Spanish.” And the payoff is great. If you know this small bit of science, you will understand why you should take metformin if you have the diagnosis of diabetes or prediabetes. You will understand more about how your disease works, what can be done about it, and why it is worth your time. Please comment if you have any questions.