2/23/2024 0 Comments Download gluco d tablet![]() Using a complex I inhibitor known as piercidin A, they found that this mechanism failed to reduce liver gluconeogenesis. ![]() To further test this hypothesis, the team performed a series of experiments both in liver slices and in mice. However, Shulman’s group has previously demonstrated that metformin only inhibits complex I at much higher pharmacological concentrations than what is typically prescribed. Most scientists previously believed that metformin works by inhibiting complex I, the first and largest of the mitochondrial complexes that creates the hydrogen ion gradient. Mitochondria in cells generate energy through the electron transport chain, which consists of four protein complexes that release energy through a series of reactions. How it accomplishes this, however, has been a mystery. Studies in humans have shown that metformin inhibits the process of gluconeogenesis, which is how the liver makes glucose from non-glucose precursors such as amino acids and lactate. “It’s important to understand how it works so we can potentially develop even better drugs to treat type 2 diabetes.” “Metformin is the most commonly used drug to treat diabetes,” says Shulman. ![]() ![]() Cowgill Professor of Medicine (Endocrinology) and professor of cellular and molecular physiology, and first author Traci LaMoia, a graduate student in Shulman’s lab, published their findings in PNAS on March 1. The team, including senior author Gerald Shulman, MD, PhD, George R. Now, Yale researchers have elucidated the mechanism behind metformin and related type 2 diabetes drugs, and debunked a previously held theory on how they work. Physicians have used the drug metformin to treat type 2 diabetes for more than half a century, but despite its prevalence, researchers have lacked a clear understanding of how it works. ![]()
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