Scientists at Northwestern University have uncovered how metformin, a common diabetes medication, lowers blood sugar levels by targeting the cell’s mitochondria. This breakthrough provides new insights into the drug’s potential for treating various diseases.
A new study from Northwestern Medicine has uncovered the mechanism behind metformin, a leading Type 2 diabetes medication known for its wide range of health benefits. The study, published in the journal Science Advances, reveals how metformin interferes with mitochondria, the cell’s “powerhouse,” to effectively lower blood sugar levels.
For over 60 years, metformin has been a staple in diabetes treatment, praised not only for its efficacy in managing blood sugar but also for slowing cancer growth, improving COVID-19 outcomes and reducing inflammation. Yet, until now, researchers struggled to pinpoint how exactly the drug functions on a cellular level.
“This research gives us a clearer understanding of how metformin works,” corresponding author Navdeep Chandel, a professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine, said in a news release.
The study, led by first author Colleen Reczek, a research assistant professor of medicine at Feinberg, demonstrated that metformin blocks a specific component known as mitochondrial complex I. This inhibition reduces the cell’s energy supply, affecting glucose levels without causing significant harm to healthy cells.
“This research significantly advances our understanding of metformin’s mechanism of action,” Chandel added. “While millions of people take metformin, understanding its exact mechanism has been a mystery. This study helps explain that metformin lowers blood sugar by interfering with mitochondria in cells.”
Historically, metformin theories have spanned across different research fields, often resulting in fragmented and indirect evidence.
Chandel added that, “Every year there’s a new mechanism, a new target of metformin and the next few years people debate those and don’t come to a consensus.”
The researchers utilized genetically engineered mice expressing a yeast enzyme, NDI1, that simulates mitochondrial complex I but is resistant to metformin’s effects. Comparison of blood glucose levels in these mice provided direct evidence of metformin’s role in inhibiting mitochondrial complex I.
“The NDI1-expressing mice were not completely resistant to its glucose-lowering effects, suggesting metformin may also target other pathways to some extent, but more research is needed,” added Chandel.
The study expands on previous research by Chandel and his collaborators. Prior studies indicated that metformin’s anti-cancer and anti-inflammatory properties could be tied to its interference with mitochondrial complex I.
“We think that the diverse effects metformin has on lowering glucose levels, decreasing inflammation and its potential anti-cancer effects could, in part, be explained by inhibiting mitochondrial complex I,” Chandel concluded. “Eventually, others will have to corroborate our idea of mitochondrial complex I inhibition as a unifying mechanism to explain how metformin could improve healthspan in humans.”
The implications of this study could be vast, potentially enhancing metformin’s application beyond diabetes treatment and offering new avenues for combating various diseases.