Breakthrough Diabetes Treatment Blocks VEGF-B Signaling
Breakthrough Diabetes Treatment Blocks VEGF-B Signaling – An international team of scientists, led from Karolinska Institutet in Sweden, has discovered an entirely new approach to the treatment of type 2 diabetes. The therapy involves the blockade of signaling by a protein known as VEGF-B and this prevents fat from accumulating in the ‘wrong’ places, such as in muscles and in the heart. As a result the cells within these tissues are once again able to respond to insulin.
In experiments on mice and rats, the scientists have managed to both prevent the development of type 2 diabetes and reverse the progression of established disease. The study is published in the journal Nature, where it is described as a breakthrough in diabetes research. The findings are the result of a joint effort by Karolinska Institutet, the Ludwig Institute for Cancer Research and the Australian biopharmaceutical company CSL Limited, amongst others.
Professor Ulf Eriksson of the Department of Medical Biochemistry and Biophysics at Karolinska Institutet says, “We discovered VEGF-B back in 1995… 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 2 diabetes, and that this can be done with a drug candidate.”
Type 2 diabetes is normally preceded by insulin resistance caused by obesity. When this happens, the cells no longer respond sufficiently to insulin, which leads to elevated levels of blood sugar (hyperglycemia). Insulin resistance is related to the storage of fat in the ‘wrong’ places, such as the muscles, blood vessels and heart, although exactly how this relationship works is not fully known. What scientists do know, however, is that the VEGF-B protein affects the transport and storage of fat in body tissue.
A total of four related studies are reported in the Nature paper. In one case, mice bred to spontaneously develop diabetes were given a drug candidate called 2H10, which is an antibody that blocks the effect of VEGF-B. The mice subsequently developed neither insulin resistance, nor diabetes. The team also crossed the diabetes strain of mice with one that lacked the ability to produce VEGF-B, and found that the offspring were protected from developing the disease.
In another two studies, the scientists took normal mice and rats that had not been specially bread to develop type 2 diabetes, and left them to develop the disease as a result of a fat-rich diet and the resulting obesity. In these cases, progression of the established disease was halted and reversed to varying degrees after treatment with 2H10.
“The results we present in this study represent a major breakthrough and an entirely new principle for the prevention and treatment of type 2 diabetes,” says Professor Åke Sjöholm, consultant in diabetology at Stockholm South General Hospital. “Existing treatments can cause many adverse reactions and their effects normally wear off. There is a desperate need for new treatment strategies for type 2 diabetes.”
Current treatments for type 2 diabetes normally involve initial dietary measures and/or pills designed to boost insulin secretion and sensitivity or to reduce glucose production. After a few years, such treatments eventually prove inadequate for up to 30 per cent of patients, who then require insulin injections. Type 2 diabetes is reaching epidemic proportions, and according to the World Health Organization, is expected to afflict over half a billion people by 2030.
Drug therapies nearly always either block or force the body’s natural processes. This is not necessarily always bad, but we prefer to take the most natural course possible, which we believe is via diet and lifestyle changes. It is never too late to start, but starting before diagnosis of diabetes is best. The longer lifestyle changes are delayed, the more damage is done by hyperglycemia and the more difficult it becomes to reverse that damage.
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