By blocking VEGF-B, a signaling protein, fat does not accumulate in muscles and the heart, and the cells within those tissues can respond properly to insulin again, researchers from the Karolinska Institute, Sweden, the Ludwig Institute for Cancer Research, based in New York, and the Australian biopharmaceutical company CSL Limited reported in the journal Nature.

Professor Ulf Eriksson and team carried out experiments on rats and mice, and managed to prevent type II diabetes from developing in the first place, as well as reversing disease progression in animals with established diabetes type II. Nature has described this finding as a "breakthrough in diabetes research".

Professor Ulf Eriksson, of the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, said:

"It's a great feeling to present these results. We discovered VEGF-B back in 1995, and since then the VEGF-B project has been a lengthy sojourn in the wilderness, but now we're making one important discovery after the other. In this present study we've shown that VEGF-B inhibition can be used to prevent and treat type II diabetes, and that this can be done with a drug candidate."

Typically, type II diabetes occurs after a person becomes obese, then insulin resistance occurs - the diabetes comes next. When this occurs, the cells do not respond properly to insulin, meaning that glucose does not enter the cells and blood glucose (sugar) levels rise. When fat is stored in the "wrong" places in the body, insulin resistance is much more likely to occur. The wrong places include the blood vessels, heart and muscles. Experts are not sure exactly how the association works.

Insulinresistance
With insulin resistance, not enough glucose enters the cells - it accumulates in the bloodstream, resulting in high blood sugar

We do know that a protein called VEGF-B impacts on the transport and storage of fat in body tissue. Prof Eriksson's research group found out about this in 2010 and published a report in the same journal. In the latest experiment, the scientists managed to block the VEGF-B signaling in laboratory rats and mice.

2H10 either prevented diabetes from occurring or reversed it

Nature reported on four related studies. In one, diabetes-induced mice were given 2H10, a drug candidate which is an antibody that inhibits the actions of VEGF-B. The mice, which were specifically bred to spontaneously develop diabetes, neither developed insulin resistance nor diabetes. The scientists crossed the mice with diabetes with mice that could not produce VEGF-B - they found that their pups never developed diabetes.

In two different studies, they used rats and mice that had not been specifically bred to develop type II diabetes. They were fed a high-calorie, fat-rich diet and became obese. The animals' natural progression to diabetes was stopped, and also reversed to varying degrees after they were treated with 2H10.

Professor Åke Sjöholm, a consultant diabetologist at Stockholm South General Hospital, Sweden, said:

"The results we present in this study represent a major breakthrough and an entirely new principle for the prevention and treatment of type II diabetes. Existing treatments can cause many adverse reactions and their effects normally wear off. There is a desperate need for new treatment strategies for type II diabetes."

The most common treatment for type II diabetes today involves initially placing the patient on a special diet; sometimes they may need to take pills which increase insulin secretion and also make the cells more sensitive to insulin. Occasionally they are given tablets to bring down the production of glucose. However, after a few years, for about one-third of all patients these treatments gradually lose their efficacy, and insulin injections are needed.

The most effective treatment today to prevent diabetes type II onset among very obese patients is bariatric surgery.

Diabetes type II is seen today by many as a serious global health problem - some describe it as an epidemic. By the end of 2030 over half-a-billion people are expected to be living with diabetes type II globally.

The experimental medicine, 2H10, is a monoclonal antibody (an antibody produced by a single clone of cells) which is being developed by CSL Limited, an Australian biopharmaceutical company.

Written by Christian Nordvist