Breakthrough for new diabetes treatmentSeptember 28, 2012
An international team of scientists, led from Karolinska Institutet in Sweden, have discovered an entirely new approach to the treatment of type II diabetes. The therapy involves the blockade of signalling 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 II diabetes and reverse the progression of established disease. The study is published in the prestigious scientific 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.
"It's a great feeling to present these results," says Professor Ulf Eriksson of the Department of Medical Biochemistry and Biophysics at Karolinska Institutet. "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."
Type II 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. 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. This was discovered by Professor Ulf Eriksson's research group in a study published in Nature in 2010. These theories have now been developed for a new study in which VEGF-B signalling was blocked in a group of diabetic mice and rats.
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 II 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 II diabetes," says Professor Ĺke 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 II diabetes."
Current treatments for type II 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 II diabetes is reaching epidemic proportions, and according to the World Health Organisation, is expected to afflict over half a billion people by 2030.
The drug candidate used in the study, 2H10, is a monoclonal antibody and is being developed by the biopharmaceutical company CSL Limited. Scientists from CSL contributed to the work and the company co-funded the study. Funding was also supplied by the Ludwig Institute for Cancer Research, the Frans Wilhelm and Waldemar von Frenckell Fund, the Wilhelm and Else Stockmann Foundation, the Novo Nordisk Foundation, the Swedish Cancer Society, the Swedish Research Council, the Torsten and Ragnar Söderberg Foundations, the Research Foundation of the Swedish Diabetes Association (Diabetesfonden), the Peter Wallenberg Foundation for Economics and Technology, and the Swedish Heart-Lung Foundation.
Earlier this year, Professor Eriksson was awarded the Heart-Lung Foundation's grand research grant of SEK 15 million (about 1.7 million / $ 2.3 million) the largest in Sweden in the field of cardiovascular disease. The grant will be used to finance further research into VEGF-B.
Related Diabetes Current Events and Diabetes News Articles
Leaky blood-brain barrier linked to Alzheimer's disease
Researchers using contrast-enhanced MRI have identified leakages in the blood-brain barrier (BBB) of people with early Alzheimer's disease (AD), according to a new study published online in the journal Radiology.
Researchers suggest whole-person perspective is needed to assess obesity
Authors from the Cleveland Clinic's Bariatric and Metabolic Institute recommend physicians use obesity staging models to recognize and manage weight-related health issues that may not be captured by traditional diagnosis criteria.
Autism care improved, diagnosis time shortened by new MU program
Wait lists for a specialist to confirm an autism diagnosis can be agonizing and last months. As the prevalence of autism and autism spectrum disorders increase, so does the demand for a health care system that is fully equipped to respond to the complex needs associated with autism.
Novel type 2 diabetes risk model more accurately assesses disease trajectory
An innovative model for determining a person's risk of developing type 2 diabetes (T2D) overcomes many of the challenges associated with estimating the onset of a chronic condition based on the usual sequence of comorbid conditions that lead up to a diagnosis of T2D.
Newly discovered gene regulates hyperglycemia-induced beta cell death in type 2 diabetes
It's no secret that over time, elevated levels of blood glucose (hyperglycemia) can induce the death of the pancreatic beta cells.
Study show female heart patients less likely to get blood thinning therapy
Female atrial fibrillation patients are less likely than their male counterparts to receive blood thinning therapies to prevent stroke, say University of Cincinnati College of Medicine researchers.
Ancient anti-inflammatory drug salicylic acid has cancer-fighting properties
Scientists from the Gladstone Institutes have identified a new pathway by which salicylic acid--a key compound in the nonsteroidal anti-inflammatory drugs aspirin and diflunisal--stops inflammation and cancer.
New study uncovers mechanisms underlying how diabetes damages the heart
Cardiac complications are the number one cause of death among diabetics. Now a team of scientists has uncovered a molecular mechanism involved in a common form of heart damage found in people with diabetes.
PNNL helps lead national microbiome initiative
Scientists at the U.S. Department of Energy's Pacific Northwest National Laboratory are playing a central role as the nation devotes more than $500 million to understand communities of microorganisms and their role in climate science, food production and human health.
Study finds one third of children have higher levels of cardiometabolic risk factors due to family history
A new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that children with a strong family history of cardiovascular disease (CVD) and/or type 2 diabetes were found to have cholesterol levels significantly higher than children with no family history of those conditions.
More Diabetes Current Events and Diabetes News Articles