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Rachel V Thomas

Metformin Controls Blood Sugar With Help From Brain Neurons, Finds Study

Metformin has remained the safe and most effective first-line treatment for Type 2 diabetes for the last 60 years. The anti-diabetic drug has been known to work through the liver and gut to lower blood sugar levels and improve the way the body handles insulin.

However, a new study has, for the first time, shown that metformin probably works through the brain, and neurons in a specific region boost its anti-diabetic effects.

The findings open up potential for more targeted and effective diabetes therapies as well as for improving brain health.

The international team of researchers led by those at Baylor College of Medicine, in the US, decoded a brain-based pathway involved in metformin's ability to lower blood sugar.

They found that the widely used diabetes medication switches off a key protein and activates specific neurons, and lowers blood sugar through a previously hidden pathway.

"Metformin is not just working in the liver or the gut, it's also acting in the brain. We found that while the liver and intestines need high concentrations of the drug to respond, the brain reacts to much lower levels," said corresponding author Dr. Makoto Fukuda, associate professor of pediatrics - nutrition at Baylor.

The new study, published in Science Advances, targeted a small protein called Rap1 -- located in a brain region known as the ventromedial hypothalamus (VMH).

Mice studies proved that metformin fights blood sugar by suppressing the activity of Rap1 in VMH.

To prove the findings, the team deployed genetically engineered mice without Rap1 in the brain.

In mice with a high-fat diet that models type 2 diabetes, low doses of metformin did not improve their blood sugar levels. 

On the contrary, when metformin was delivered in very small amounts directly into the brains of diabetic mice, it effectively lowered blood sugar levels.

Further, the team found that SF1 neurons located in the VMH are helping metformin to fight diabetes. 

When the team measured the electrical activity of these neurons, they found that metformin’s activity increased only when Rap1 was present

The findings demonstrated that Rap1 is required for metformin to activate these brain cells and regulate blood sugar. 

"This discovery changes how we think about metformin," Dr. Fukuda said.

Also read: <a href="https://www.healthandme.com/health-news/indian-drug-regulator-flagged-90-combination-medicines-sold-without-approval-article-153897557" data-type="tilCustomLink">Indian Drug Regulator Flagged 90 Combination Medicines Sold Without Approval</a>

Metformin has also shown potential to boost fertility levels in people with polycystic ovary syndrome (PCOS) -- a condition that affects how the ovaries work.

Metformin treats PCOS by lowering insulin and blood sugar levels. This can also improve ovulation and encourage regular periods.

Metformin has previously shown its potential for slowing <a href="https://www.healthandme.com/health-wellness/metformin-medicine-used-to-treat-type-2-diabetes-can-make-you-look-younger-studies-find-article-151039623" data-type="tilCustomLink">brain aging</a> and improve lifespan.

While metformin is safe for most adults and children aged 10 years and older, the drug may not suitable for some people. this includes people who:

<ul><li>have ever had an allergic reaction to metformin or other medicine</li><li>have uncontrolled diabetes</li><li>have liver or kidney problems</li><li>have a severe infection</li><li>are being treated for heart failure or have recently had a heart attack.</li></ul>

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Metformin has remained the safe and most effective first-line treatment for Type 2 diabetes for the last 60 years. The anti-diabetic drug has been known to work through the liver and gut to lower blood sugar levels and improve the way the body handles insulin. However, a new study has, for the first time, shown that metformin probably works through the brain, and neurons in a specific region boost its anti-diabetic effects. The findings open up potential for more targeted and effective diabetes therapies as well as for improving brain health. The international team of researchers led by those at Baylor College of Medicine, in the US, decoded a brain-based pathway involved in metformin's ability to lower blood sugar. They found that the widely used diabetes medication switches off a key protein and activates specific neurons, and lowers blood sugar through a previously hidden pathway. "Metformin is not just working in the liver or the gut, it's also acting in the brain. We found that while the liver and intestines need high concentrations of the drug to respond, the brain reacts to much lower levels," said corresponding author Dr. Makoto Fukuda, associate professor of pediatrics - nutrition at Baylor. Metformin: New Brain Pathway The new study, published in Science Advances, targeted a small protein called Rap1 -- located in a brain region known as the ventromedial hypothalamus (VMH).  Mice studies proved that metformin fights blood sugar by suppressing the activity of Rap1 in VMH. To prove the findings, the team deployed genetically engineered mice without Rap1 in the brain.In mice with a high-fat diet that models type 2 diabetes, low doses of metformin did not improve their blood sugar levels. On the contrary, when metformin was delivered in very small amounts directly into the brains of diabetic mice, it effectively lowered blood sugar levels. Further, the team found that SF1 neurons located in the VMH are helping metformin to fight diabetes. When the team measured the electrical activity of these neurons, they found that metformin’s activity increased only when Rap1 was present The findings demonstrated that Rap1 is required for metformin to activate these brain cells and regulate blood sugar. "This discovery changes how we think about metformin," Dr. Fukuda said. Also read: Indian Drug Regulator Flagged 90 Combination Medicines Sold Without ApprovalMetformin: Other benefitsMetformin has also shown potential to boost fertility levels in people with polycystic ovary syndrome (PCOS) -- a condition that affects how the ovaries work. Metformin treats PCOS by lowering insulin and blood sugar levels. This can also improve ovulation and encourage regular periods. Metformin has previously shown its potential for slowing brain aging and improve lifespan. While metformin is safe for most adults and children aged 10 years and older, the drug may not suitable for some people. this includes people who:have ever had an allergic reaction to metformin or other medicinehave uncontrolled diabeteshave liver or kidney problemshave a severe infectionare being treated for heart failure or have recently had a heart attack.

metformin controls blood sugar with help from brain neurons, finds study

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