Computer simulations identify chemical key to diabetes drug alternatives

June 5, 2018, University of Tennessee at Knoxville
Jeremy Smith is the 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. Credit: University of Tennessee, Knoxville

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 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 .

"This 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.

Explore further: Team unlocks secrets of diabetes drug: How and why metformin needs to interact with insulin to be effective

More information: Min Pi et al. Computationally identified novel agonists for GPRC6A, PLOS ONE (2018). DOI: 10.1371/journal.pone.0195980

Related Stories

Team unlocks secrets of diabetes drug: How and why metformin needs to interact with insulin to be effective

November 3, 2013
About 120 million people around the world with Type 2 diabetes – and two million in Canada – take the drug metformin to control their disease.

New strategy to lower blood sugar may help in diabetes treatment

September 3, 2015
Some treatments for type 2 diabetes make the body more sensitive to insulin, the hormone that lowers blood sugar. But new research at Washington University School of Medicine in St. Louis suggests a different strategy: slowing ...

Metformin beats other type 2 diabetes drugs for first treatment: study

October 28, 2014
(HealthDay)—People newly diagnosed with type 2 diabetes who are initially given the drug metformin are less likely to eventually need other drugs to control their blood sugar, a new study suggests.

Study: Most-used diabetes drug works in different way than previously thought

January 6, 2013
A team, led by senior author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Medicine, with the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, ...

Study reverses current thought on treatment of cirrhosis

June 19, 2014
Researchers at Mayo Clinic released a new study reversing current thought on the treatment of cirrhotic patients with type 2 diabetes. The study found that the continuation of metformin after a cirrhosis diagnosis improved ...

Two compounds target the gut to lower blood sugar, in obese or diabetic rats

April 6, 2015
Researchers at the Toronto General Hospital Research Institute have discovered metformin (the most widely prescribed type 2 diabetic medication) and resveratrol, a compound found in red wine, trigger novel signaling pathways ...

Recommended for you

Weight gain after smoking cessation linked to increased short-term diabetes risk

August 15, 2018
People who gain weight after they quit smoking may face a temporary increase in the risk of developing type 2 diabetes, with the risk directly proportional to the weight gain, according to a new study from Harvard T.H. Chan ...

Evening preference, lack of sleep associated with higher BMI in people with prediabetes

August 15, 2018
People with prediabetes who go to bed later, eat meals later and are more active and alert later in the day—those who have an "evening preference"—have higher body mass indices compared with people with prediabetes who ...

Healthy fat cells uncouple obesity from diabetes

August 14, 2018
About 422 million people around the world, including more than 30 million Americans, have diabetes. Approximately ninety percent of them have type 2 diabetes. People with this condition cannot effectively use insulin, a hormone ...

'Alarming' diabetes epidemic in Guatemala tied to aging, not obesity

August 14, 2018
The diabetes epidemic in Guatemala is worse than previously thought: more than 25 percent of its indigenous people, who make up 60 percent of the population, suffer from type 2 diabetes or pre-diabetes, suggests a new study ...

Gut reaction linked to type 1 diabetes

August 13, 2018
Understanding the link between diabetes and the gut could lead to the development of new therapies to delay the onset of type 1 diabetes, according to University of Queensland researchers.

Early age of type 1 diabetes diagnosis linked to shorter life expectancy, compared to later diagnosis

August 10, 2018
Life-expectancy for individuals with younger-onset disease is on average 16 years shorter compared to people without diabetes, and 10 years shorter for those diagnosed at an older age

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.