The body relies on glucose as a fast and versatile fuel, but too much glucose can lead to insulin resistance and ultimately damage blood vessels and organs. The study found metformin slows mitochondrial energy production in gut cells, forcing the intestine to metabolize extra sugar.
"Metformin essentially helps the intestine suck the glucose out of the bloodstream, which further highlights that the gut plays a major role in regulating blood sugar levels," said corresponding author Navdeep Chandel, professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.
The study is published in Nature Metabolism.
The study builds off findings from previous work in Chandel's lab, which found metformin lowers blood sugar by blocking a specific part of the cell's energy-making machinery called mitochondrial complex I, a key enzyme in cellular respiration.
The new study furthers that work by pinpointing the specific tissue targeted by metformin. The findings suggest directing drugs or supplements to the gut could be an effective strategy for controlling blood sugar, Chandel said.
Chandel is also the David W. Cugell, MD, Professor of Medicine (Pulmonology and Critical Care), Biochemistry and Molecular Genetics and an investigator with the Chan Zuckerberg Initiative. The study's first author is Zach Sebo, a postdoctoral fellow in the Chandel lab who will soon start his own research group at the University of Kansas School of Medicine.
"Our study suggests that revisiting assumptions about metformin's mechanism may offer a more detailed understanding of how it works," Sebo said.
