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Protein may help control diabetes symptoms

10:25am Thursday 17th July 2014 content supplied byNHS Choices

"Diabetes could be cured 'in single jab'," is the misleading headline in the Daily Express. The news comes from an exciting new mouse study which found promising results for a treatment for type 2 diabetes.

However, the study did not show that it would cure diabetes, and certainly not after a single injection.

Researchers performed experiments in mice using a protein called fibroblast growth factor 1 (FGF1). FGF1 works in a similar way to an existing class of diabetes drugs called thiazolidinediones by making the body's cells more sensitive to insulin-reducing blood sugar levels.

Unfortunately, using thiazolidinediones in humans causes side effects such as weight gain, which can be problematic in patients who are often already overweight.

Researchers found repeated injections of FGF1 every other day for 35 days in mice improved their insulin sensitivity and lowered blood sugar levels without any noticeable side effects. However it is unlikely there would be no side effects in humans.

It is too early to say this would be a "cure" for diabetes, and further research is required before human trials are conducted. This is a promising new avenue of study, however.

 

Where did the story come from?

The study was carried out by researchers from the Salk Institute for Biological Studies, New York University School of Medicine, and the University of California, San Diego, in the US, the University of Groningen in the Netherlands, and the Westmead Millennium Institute and the University of Sydney in Australia.

It was funded by the US National Institutes of Health, the Glenn Foundation for Medical Research, the Australian National Health and Medical Research Council, the European Research Council, and several US and Dutch foundations and research organisations.

The study was published in the peer-reviewed journal, Nature.

The Daily Express' headline claiming this study could lead to a diabetes cure was inappropriate and not supported by the study's findings.

The Daily Mail and Daily Mirror's coverage was more restrained, and the Mirror print edition included a useful diagram explaining how the treatment could work in humans.

There are, however, some inaccurate reports the treatment reverses insulin resistance. This was not shown in the study - the treatment improved insulin sensitivity by about 50%. This is not the same thing as reversing insulin resistance.

 

What kind of research was this?

This was a series of laboratory and animal experiments that aimed to see if a protein normally present in mammals called fibroblast growth factor 1 (FGF1) could reduce high blood glucose (sugar) levels.

The FGF1 protein is known to have a role in new blood vessel formation (angiogenesis) and cell division, and is also thought to be involved in organ development. It has been used in human studies as a treatment for peripheral vascular disease.

Scientists have suspected FGF1 is also involved in the regulation of blood glucose levels, as genetically modified mice that do not have this protein develop insulin resistance when they are given a high-fat diet.

The hormone insulin is required for cells to take in glucose for energy. When insulin resistance occurs, there is a reduction in the ability of cells to take in glucose. This can lead to type 2 diabetes. The researchers wanted to see if the insulin resistance could be reversed by giving mice FGF1.

 

What did the research involve?

The researchers conducted a variety of experiments to investigate the effects of FGF1 on blood glucose levels in mice.

They gave a single injection of recombinant FGF1 (rFGF1) from rodents into diabetic mice and normal mice, and then measured their blood glucose levels.

The researchers also injected recombinant human FGF1 to see if it had the same effect. They injected other types of fibroblast growth factors, such as FGF2, FGF9 and FGF10, into diabetic mice and then measured blood glucose levels.

The researchers performed repeated injections of rFGF1, one every other day for 35 days, assessed the effects on blood glucose and insulin sensitivity, and monitored the mice for side effects.

They investigated whether the effects were related to rFGF1 increasing the levels of insulin being released, or whether it was using a different mechanism. This also involved injecting mice that could not produce insulin (similar to type 1 diabetes).

Another aspect of the study investigated whether the researchers could modify the rFGF1 to stop it causing unwanted cell division, but still be able to reduce blood glucose levels. They did this by removing some of the amino acids in the protein and testing it in the laboratory and then in mice.

 

What were the basic results?

A single injection of rFGF1 into diabetic mice reduced their high blood sugar levels to normal levels with a maximum effect between 18 and 24 hours. The effect lasted for more than 48 hours. Blood sugar levels did not go dangerously low (hypoglycaemia).

Similar results were found if the injection was into the bloodstream or the peritoneal cavity (the space around abdominal organs).

When normal mice were injected, there was no change in blood sugar level. Other types of FGF proteins did not reduce blood sugar levels. Human rFGF1 injections were also found to work in the mice.

Repeated injections of rFGF1 improved the ability of skeletal muscle to take in glucose, indicating it improved the cells' sensitivity to insulin.

The fasting blood glucose level of the mice was 50% lower than mice given a control injection with saline. Insulin tolerance test (ITT) results also improved, showing the mice had become more sensitive to insulin again.

The mice did not gain weight, their livers did not become fatty, and there was no bone loss with the treatment, all side effects of current therapies that aim to improve insulin sensitivity, such as thiazolidinediones.

The mice appeared to have normal activity levels and breathing rates. FGF1 did not make the pancreas release more insulin in laboratory or mouse experiments.

In mice without the ability to produce insulin (similar to type 1 diabetes), rFGF1 did not reduce their blood sugar levels. However, it did improve the level of blood sugar reduction when insulin was then injected.

These results suggest that rFGF1 may cause cells to become more sensitive to insulin.

Removing some of the amino acids from rFGF1 stopped it inducing cell division in laboratory experiments, but it was still able to reduce blood sugar levels in the mice.

 

How did the researchers interpret the results?

The researchers concluded they have uncovered an unexpected action of human FGF1, which they say has "therapeutic potential for the treatment of insulin resistance and type 2 diabetes".

 

Conclusion

This exciting study has shown potential for rFGF1 to become a treatment for both type 1 and type 2 diabetes. The mouse studies have shown that for type 2 diabetes, rFGF1 reduces blood glucose levels in a sustained manner, and its prolonged use improves insulin sensitivity.

There is also potential for rFGF1 to improve blood glucose control for type 1 diabetes, though it would not replace the requirement for insulin injections.

The researchers have also shown they can modify rFGF1 so it doesn't cause unwanted cell division in laboratory experiments.

But further investigations are needed to see whether this version only has an effect on blood glucose levels or whether it retains its other known functions, such as new blood vessel formation, which may potentially cause side effects.

Encouragingly, the researchers did not find any side effects with the treatment, but it was only given over a maximum of 35 days.

Further research will be required before human trials are conducted, but this is a promising new avenue of study.

Even if any drug that stems from this research did prove to be effective and safe in humans, it is unlikely it would lead to a permanent cure for diabetes. It is more likely it would become a maintenance treatment a person would need to take long term on a regular basis.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Summary

"Diabetes could be cured 'in single jab'," is the misleading headline in the Daily Express. The news comes from an exciting new mouse study that found promising results for a treatment for type 2 diabetes. But the study did not show that it would cure.

Links to Headlines

Diabetes could be cured 'in single jab'. Daily Express, July 17 2014

Protein discovery that could reverse the damage of diabetes: Breakthrough could lead to cheap drug that would halt disease. Daily Mail, July 17 2014

Diabetes breakthrough drug can work for two days from a single jab. Daily Mirror, July 16 2014

Links to Science

Suh JM, Jonker JW, Ahmadian M, et al. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature. Published online July 16 2014

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