Common Frontline Diabetes Drug Reverses Inflammation in Liver

In new development, researchers have found that a common diabetes medication can reverse liver inflammation. The research findings were published in the journal of Gene and Development, Thursday.

Metformin, is a frontline treatment drug for type-2-diabetes, globally used by vast majority of people. A research team at Silk Institute explains how an enzyme, protein in nature, holds significance within the human’s body and essential for metformin’s function. Furthermore, it was showed that enzyme proteins regulates by metformin, modulates the inflammation; a new aspect for which drug has not been explained before.

Metformin drug is derived from a plant called lilac, that has medicinal properties and has been used for centuries. The exact underlying mechanism of how it controls blood glucose remains unclear and needs further elucidation.

The drug is globally used to treat type-2-diabetes, an ailment where body does not produce sufficient insulin and polycystic ovary syndrome (PCOS), an illness that affects how the ovaries work.

Metformin works by lowering blood sugar levels your liver releases into your blood and improves the response of body towards insulin- sugar controlling hormone in blood. Metformin also reduces blood sugar and insulin levels and promote ovulation in PCOS.

It is advised to take the medicine with meals to reduce the side effects including lethargy, feeling of sickness, diarrhoea, and stomach-ache. Moreover, it does not cause weight gain like other diabetic drugs.  Most common brand names in market are Bolamyn, Diagemet, Glucient, Glucophage and Metabet. Liquid metformin comes under the brand name Riomet.

Source: CDC

Previously, it is known from literature, that AMPK protein is activated by metformin. It works by energy conservation when nutrients are low and once its activated, it starts a chain of effects in regulating two proteins called Raptor and TSC2, which subsequently blocks growth promoting mTORC1 complex that helps in tumour growth. This explains metformin role in tumour prevention. It is also being used for anti-aging clinical trials in United States right now.

Researchers studied the effect of metformin by blocking the AMPK protein. After analysis the genetic profile in liver, it was found that after AMPK blockage, it couldn’t generate the cascade effect, hence no transfer signal found to activate Raptor or TSC2. This resulted in blocking effect of metformin on hundreds of genes.

Scientists explained that some of these blocked genes were essential for the lipid (fat) metabolism. However, many other genes were associated with inflammation. The genetic data reveals that Metformin commonly turned on anti-inflammatory pathways, which requires chain events of AMPK, TSC2 and Raptor.

“We didn’t go looking for a role in inflammation, so for it to come up so strongly was surprising,” says Salk postdoctoral fellow and first author Jeanine Van Nostrand.

Diabetic individuals with obesity most commonly exhibit chronic inflammation which is the major culprit in poor wound healing and recovery and is believed to be associated with heart disease and stroke.

Therefore, it is imperative to find the potential role of metformin, its interrelationship between AMPK and mTORC, and its role in managing both blood glucose level and inflammation.

“If turning on AMPK and shutting off mTORC1 are responsible for some of the systemic benefits of exercise, that means we might be able to better mimic this with new therapeutics designed to mimic some of those effects,” says senior author, Reuben Shaw, a professor in Salk’s Molecular and Cell Biology Laboratory.

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