Metformin Slows Mitochondrial Energy Production, Promotes Glycemic Control - News Center

"For decades, physicians and scientists thought metformin, the leading Type 2 diabetes medication taken by millions worldwide, mainly targets the liver to suppress glucose production. But a new Northwestern study in mice, published in Nature Metabolism, has found this "wonder drug" instead focuses primarily on the gut, acting to prevent glucose levels rising in the blood by driving glucose utilization inside cells lining the intestine."

"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, PhD, professor of Biochemistry and Molecular Genetics."

"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 also is the David W. Cugell, MD, Professor of Medicine in the Division of Pulmonology and Critical Care, and an investigator with the Chan Zuckerberg Initiative."

Metformin is widely used for Type 2 diabetes. Findings in mice show metformin primarily targets gut cells rather than mainly acting on the liver. Metformin slows mitochondrial energy production in intestinal cells by blocking mitochondrial complex I. This change forces the intestine to metabolize excess glucose instead of allowing glucose to remain in the bloodstream. By increasing glucose utilization in the gut, metformin helps prevent blood glucose levels from rising. The results indicate that the gut plays a major role in regulating blood sugar. Targeting the gut with drugs or supplements could be an effective strategy for controlling blood sugar levels.

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