The diabetes drug metformin — derived from a lilac plant that’s been used medicinally for more than a thousand years — has been prescribed to hundreds of millions of people worldwide as the frontline treatment for type 2 diabetes.
Yet scientists don’t fully understand how the drug is so effective at controlling blood glucose.
In a new study from the Salk Institute, researchers found the importance of specific enzymes in the body for metformin’s function.
In addition, they showed that the same proteins, regulated by metformin, controlled aspects of inflammation in the liver, something the drug has not typically been prescribed for.
Researchers have known for 20 years that metformin activates a metabolic master switch, a protein called AMPK, which conserves a cell’s energy under low nutrient conditions, and which is activated naturally in the body following exercise.
These findings helped explain the ability of metformin to inhibit the growth of tumors.
In the study, the team found that in the liver, when AMPK couldn’t communicate with Raptor or TSC2, metformin’s effect on hundreds of genes was blocked.
Some of these genes were related to lipid (fat) metabolism, helping explain some of metformin’s beneficial effects. But surprisingly, many others were linked to inflammation.
Metformin, the genetic data showed, normally turned on anti-inflammatory pathways and these effects required AMPK, TSC2 and Raptor.
People suffering from obesity and diabetes often exhibit chronic inflammation, which further leads to additional weight gain and other maladies including heart disease and stroke.
Therefore, identifying an important role for metformin in the control of both blood glucose and inflammation reveals how metformin can treat metabolic diseases by multiple means.
Metformin and exercise elicit similar beneficial outcomes, and research has previously shown that AMPK helps mediate some of the positive effects of exercise on the body.
The team says if turning on AMPK is responsible for some of the systemic benefits of exercise, that means scientists might be able to better mimic this with new therapeutics designed to mimic some of those effects.
In the meantime, the findings suggest that researchers should study the potential use of metformin in inflammatory diseases, particularly those involving liver inflammation.
If you care about liver health, please read studies about how to have better liver health and findings of common dietary supplements could harm your liver health.
For more information about liver disease prevention and treatment, please see recent studies about why men are easier to develop liver cancer and results showing that aspirin may help cut risk of liver cancer.
The study is published in Genes & Development. One author of the study is Reuben Shaw.
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