Nav: Home

Computer simulations identify chemical key to diabetes drug alternatives

June 05, 2018

Jeremy Smith, Governor's Chair for Molecular Biophysics at the University of Tennessee, Knoxville, and director of the Center for Molecular Biophysics at Oak Ridge National Laboratory, has worked with a research team from the UT Health Science Center to discover a chemical compound that could lower sugar levels as effectively as the diabetes drug metformin but with a lower dose.

Smith, together with Jerome Baudry, of the University of Alabama at Huntsville, and graduate student Karan Kapoor, of the University of Illinois at Urbana-Champaign, used high-performance computing to create sophisticated simulations to suggest chemicals that could activate GPRC6A, a protein that regulates sugar levels by simultaneously correcting abnormalities in pancreatic insulin secretion, glucose uptake into skeletal muscle, and liver regulation of glucose and fat metabolism. The UTHSC team verified its potency and used this starting point to design an even more effective chemical.

"This chemical compound lowers sugar levels in mice as effectively as metformin, but with a 30-times lower dose," Smith said. "It therefore is a good starting point for the development of a new and effective drug to fight diabetes."

This new approach to diabetes drug discovery has been published in PLOS One, a peer-reviewed open access scientific journal.

Leading the UTHSC research team is Darryl Quarles, UT Medical Group Endowed Professor of Nephrology, director of the Division of Nephrology, and associate dean for Research in the College of Medicine at UTHSC.

With more than 400 million people suffering from Type 2 diabetes worldwide, the global cost of medicine and prevention is close to a trillion dollars annually. Metformin, a drug that lowers the liver's production of sugar and decreases risk of mortality, is currently recommended as a first-line treatment. However, there is a need for alternative treatment options when patients are not responsive to metformin.

Smith's computations found several chemicals that might activate the protein, and the Quarles laboratory at UTHSC tested each. A team of UTHSC medicinal chemists then used the results to synthesize related molecules for pre-clinical testing, and a chemical called DJ-V-159 was found to be highly potent in stimulating insulin secretion and lowering sugar levels in mice.
-end-
CONTACT:

Karen Dunlap, UT Knoxville (865-974-8674, kdunlap6@utk.edu)

Connor Bran, UT Health Science Center (901-448-2517, cbran@uthsc.edu)

University of Tennessee at Knoxville

Related Metformin Articles:

Diabetes drug study explores cardiovascular risks for patients with kidney disease
Among the 30 million U.S. adults with Type 2 diabetes, 20% have impaired kidney function.
LSU Health research targets metformin as breast cancer prescription
Research conducted by Suresh Alahari, PhD, Professor of Biochemistry and Genetics at LSU Health New Orleans School of Medicine, has found that metformin, a commonly prescribed drug for Type 2 Diabetes, may be effective in treating cancers that lack a protein called Nischarin.
Comparing major adverse cardiovascular events among patients with diabetes, reduced kidney function treated with metformin or sulfonylurea
This observational study compared major cardiovascular events (including hospitalization for heart attack, stroke, transient ischemic attack or cardiovascular death) among patients with diabetes and reduced kidney function treated with metformin or a sulfonylurea (a class of drugs to treat diabetes).
New insights into how diet & medication impact the influence of gut bacteria on our health
Research published in Cell on 29th August by the groups of Filipe Cabreiro from the MRC London Institute of Medical Sciences and Imperial College and Christoph Kaleta from Kiel University in Germany has demonstrated that diet can alter the effectiveness of a type-2 diabetes drug via its action on gut bacteria.
Metformin could lower risk of dementia in African Americans with type 2 diabetes
A large observational cohort study examining male veterans aged over 50 years with type 2 diabetes found that metformin use was associated with a significantly lower risk of dementia in African American patients.
NRG oncology trial of metformin for non-small cell lung cancer
Initial results of NRG-LU001 indicate that, although the diabetes agent metformin was well-tolerated by patients, the agent has not clearly improved progression-free survival (PFS) or overall survival (OS) for trial participants with locally advanced non-small cell lung cancer (NSCLC).
Metformin may help patients maintain weight loss long-term
In the Diabetes Prevention Program (DPP) clinical trial and its long-term follow-up study, among the persons who lost at least 5 percent of their body weight during the first year, long-term maintenance of weight loss was more likely if they had been assigned to treatment with metformin than with placebo or lifestyle intervention.
Diabetic drug shown to reduce the risk of heart disease in non-diabetic patients
Metformin could reverse the harmful thickening of heart muscle that leads to cardiovascular disease, according to researchers at the University of Dundee.
Diabetes medication may protect against a common cause of blindness
Researchers from Taiwan have shown that people with type 2 diabetes who took a common diabetes medication, metformin, had a significantly lower rate of age-related macular degeneration (AMD).
Scientists discover a new lead for mechanism of action of diabetes drug metformin
Canadian and British researchers are able to see how frontline diabetes drug metformin alters cell glucose uptake using new technology that probes how drugs act on all cellular functions.
More Metformin News and Metformin Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.