Metal binding important for metformin action

April 14, 2012
Metal binding important for metformin action
The ability of metformin to bind mitochondrial copper may be essential to its mechanism of action, according to a study published online April 9 in Diabetes.

(HealthDay) -- The ability of metformin to bind mitochondrial copper may be essential to its mechanism of action, according to a study published online April 9 in Diabetes.

Noting that the of metformin is unclear but most evidence has shown that the drug binds to , most stably to copper, rather than protein targets, Lisa Logie, Ph.D., from the University of Dundee in the United Kingdom, and colleagues interfered with the ability of metformin to bind copper and examined the impact on cellular responses.

The researchers found that copper sequestration interfered with the known effects of metformin on AMP-activated (AMPK)-dependent signaling and S6 , which were regulated independently. The metformin-copper interaction was stabilized by extensive pi-electron delocalization, which allowed regulation of AMPK, production of glucose, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding. In contrast, direct modification of the metal-liganding groups of the biguanide structure prevented regulation of S6 phosphorylation. Further studies showed that pioglitazone also targeted mitochondrial copper.

"In summary, this study indicates that effects of metformin and related compounds on cell responses depend on their ability to interact with copper," Logie and colleagues conclude. "More broadly, our results suggest that the number of targets for drug discovery could be widened not only by investigating nonprotein targets such as copper, but also by considering the role of metal-induced effects on chemical bonding and conformational geometries of drug structures."

Explore further: Research Helps Uncover the Secrets of an Age-Old Killer

More information: Abstract
Full Text (subscription or payment may be required)

Related Stories

Research Helps Uncover the Secrets of an Age-Old Killer

December 7, 2006

Scientists working in part at the Stanford Synchrotron Radiation Laboratory (SSRL) have discovered a gene for a protein that regulates the cellular response to copper in the bacterium that causes tuberculosis. Copper is a ...

Diabetes drug could work against Alzheimer's

November 24, 2010

Scientists from Berlin, Bonn and Dundee show in animal models that the diabetes drug metformin has an effect against one of the main causes of the Alzheimer's disease.

Copper + love chemical = big sulfur stink

February 6, 2012

When Hiroaki Matsunami, Ph.D., at Duke set out to study a chemical in male mouse urine called MTMT that attracts female mice, he didn't think he would stumble into a new field of study.

Diabetes drug can prevent heart disease

March 26, 2012

The widely used diabetes medicine metformin can have protective effects on the heart, reveals a new study conducted at the Sahlgrenska Academy, at the University of Gothenburg, Sweden.

Recommended for you

New study reveals a novel protein linked to type 2 diabetes

August 16, 2016

Findings from Boston University School of Medicine (BUSM), which appear in eLife, provide a possible explanation as to why most people who are obese develop insulin resistance and type 2 diabetes. A minority of obese individuals, ...

Gene variant explains differences in diabetes drug response

August 9, 2016

The first results from a large international study of patients taking metformin, the world's most commonly used type 2 diabetes drug, reveal genetic differences among patients that may explain why some respond much better ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.