Ability to chart the molecular progress of diabetes brings personalized medicine closer to realization

December 19, 2012
Obesity often triggers diabetes. The molecular changes induced by this metabolic condition, as well as the drugs used to treat it, can now be traced, paving the way to personalized therapy. Credit: iStockphoto/Thinkstock

Researchers in Singapore have succeeded in tracking, for the first time, the molecular changes caused by type 2 diabetes that affect how the body handles glucose production in the liver. In a series of experiments in mice, the researchers introduced a form of the compound pyruvate that incorporated specially treated carbon nuclei. This allowed the researchers to follow the processing of the compound using magnetic resonance spectroscopy (MRS). In this way, the team, led by Phillip Lee of the Singapore Bioimaging Consortium, showed that the enzyme pyruvate carboxylase plays a key role in the development of diabetes.

The researchers also used their technology to plot the induced by diabetes treatment over time. "This facilitates an in-depth understanding of treatment response in each subject and paves the way for personalized treatment," Lee says.

Diabetes is a consequence of the dysfunction of insulin, a hormone that stimulates of glucose from the blood. This process is closely linked to the production of glucose in the liver. Since the 1980s, limited study of the molecular details of has been possible using MRS to track organic compounds incorporating the rarer type of natural carbon known as carbon-13. Recently a 'hyperpolarized' form of carbon-13—vastly easier to detect using MRS—has become available.

Lee and his co-workers injected hyperpolarized carbon-13-labeled pyruvate into a strain of mice in which type-2 diabetes can be induced simply by changing the diet from normal to high fat. Using MRS, they then traced over time, in both normal and diabetic mice, the compounds into which the hyperpolarized carbon nuclei became incorporated, and in what proportions. Their results provide evidence not only of which are active, but also which are dominant in normal and diabetic mice.

By comparing the two groups of mice, they were able to show distinct changes in the liver metabolism of over time, particularly the importance of the biochemical pathway dependent on the enzyme pyruvate carboxylase in the development of diabetes. When the researchers gave the mice drugs typically used to treat diabetes, their technique detected the metabolic changes resulting from the therapy.

"This technology could be used to screen for metabolic disorders associated with other conditions such as heart failure, cancers and brain diseases," Lee says. "We are extending our work to investigate metabolic aberrations in the diabetic heart, and to understand the therapeutic effects of anti-diabetic drugs on cardiac function."

Explore further: Team identifies key protein causing excess liver production of glucose in diabetes

More information: Lee, P., Leong, W., Tan, T., Lim, M., Han, W. & Radda, G. K. In vivo hyperpolarized carbon-13 magnetic resonance spectroscopy reveals increased pyruvate carboxylase flux in an insulin resistant mouse model. Hepatology advance online publication, 22 August 2012 (doi: 10.1002/hep.26028). http://onlinelibrary.wiley.com/doi/10.1002/hep.26028/abstract

Related Stories

Team identifies key protein causing excess liver production of glucose in diabetes

September 28, 2011
Researchers at the John G. Rangos Sr. Research Center at Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine have identified a powerful molecular pathway that regulates the liver's ...

Research aims to prevent diabetic kidney failure

November 5, 2011
The enzyme arginase-2 plays a major role in kidney failure, and blocking the action of this enzyme might lead to protection against renal disease in diabetes, according to researchers.

Natural compound helps reverse diabetes in mice

October 4, 2011
Researchers at Washington University School of Medicine in St. Louis have restored normal blood sugar metabolism in diabetic mice using a compound the body makes naturally. The finding suggests that it may one day be possible ...

Why do the different people's bodies react differently to a high-fat diet?

April 26, 2012
Gut flora, otherwise knows as gut microbiota, are the bacteria that live in our digestive tract. There are roughly one thousand different species of bacteria, that are nourished partly by what we eat. Each person has their ...

Metabolic shift may offer early cancer clue

July 5, 2011
Cancer cells are well known for their altered metabolisms, which may help them generate the energy they need for rapid growth. Using an emerging imaging technology, researchers reporting in the July Cell Metabolism, a Cell ...

Hops compounds improve health of obese diabetic mice

March 28, 2012
A class of compounds found in hops, the crop generally known for its role in beer production, reduces weight gain in obese and diabetic mice, according to a study published Mar. 28 in the open access journal PLoS ONE.

Recommended for you

Alzheimer's drug cuts hallmark inflammation related to metabolic syndrome by 25 percent

July 20, 2017
An existing Alzheimer's medication slashes inflammation and insulin resistance in patients with metabolic syndrome, a potential therapeutic intervention for a highly dangerous condition affecting 30 percent of adults in the ...

Diabetes or its precursor affects 100 million Americans

July 19, 2017
Almost one-third of the US population—100 million people—either has diabetes or its precursor condition, known as pre-diabetes, said a government report Tuesday.

One virus may protect against type 1 diabetes, others may increase risk

July 11, 2017
Doctors can't predict who will develop type 1 diabetes, a chronic autoimmune disease in which the immune system destroys the cells needed to control blood-sugar levels, requiring daily insulin injections and continual monitoring.

Diabetes complications are a risk factor for repeat hospitalizations, study shows

July 7, 2017
For patients with diabetes, one reason for hospitalization and unplanned hospital readmission is severe dysglycemia (uncontrolled hyperglycemia - high blood sugar, or hypoglycemia - low blood sugar), says new research published ...

Researchers identify promising target to protect bone in patients with diabetes

July 7, 2017
Utilizing metabolomics research techniques, NYU Dentistry researchers investigated the underlying biochemical activity and signaling within the bone marrow of hyperglycemic mice with hopes of reducing fracture risks of diabetics

Immune system killer cells increase risk of diabetes

July 6, 2017
More than half of the German population is obese. One effect of obesity is to chronically activate the immune system, placing it under continuous stress. Researchers in Jens Brüning's team at the Max-Planck-Institute for ...

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.