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 recent study from the Salk Institute, scientists 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 diabetes, please read studies about how COVID-19 is linked to diabetes, and scientists find new way to detect fatty liver disease accurately.
For more information about nutrition, please see recent studies that Keto diet could benefit overweight people with type 2 diabetes, and results showing Mediterranean diet could help reduce the diabetes risk by 30%.
The study was published in Genes & Development and conducted by Reuben Shaw et al.
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