Page last updated at 23:13 GMT, Wednesday, 16 July 2008 00:13 UK

Diabetes limb loss 'could be cut'

Diabetes injection
Diabetes can cause gangrene and ulcers

A discovery by scientists may help reduce the risk of people with diabetes losing a limb.

Circulatory complications can lead to leg ulcers and gangrene so severe that limb amputation is the only answer.

Work by the University of Bristol has pinpointed a protein in cells which could be responsible.

It is hoped it could lead to drug treatment to reduce the number of Britons who lose a limb to diabetes from the current 100 each week.

A treatment would have enormously beneficial effects on one of the most devastating and life-threatening complications of diabetes
Professor Peter Weissberg
British Heart Foundation

Diabetes, if not properly treated, can lead to a restricted blood supply to the tissues and a reduced capacity to recover from injury due to the body's inability to grow new blood vessels to speed the healing process.

This can leave limbs, in particular the legs and feet, vulnerable to ulcers and gangrene.

The Bristol team, whose work on mice is featured online in Circulation Research, focused on a protein receptor called p75NTR.

It is not found in the cells that line healthy blood vessels which are able to heal rapidly from injury.

However, diabetes causes these cells to start producing p75NTR and this appears to undermine the ability to grow the new blood vessels necessary to drive the healing process.

Receptor gene

The Bristol team were able to confirm this by showing that, if the receptor gene was put into healthy blood vessel cells, they became dysfunctional.

Equally, they showed that injecting the gene into healthy muscle and then restricting blood supply caused impaired healing following injury identical to that seen in diabetes.

Finally, the researchers inhibited the p75NTR receptor in diabetic mice before restricting the blood supply to one of their limbs.

Inhibition enabled the limb to recover from the restricted blood flow well.

The receptor appears to depress the cell's normal signalling mechanisms that are necessary to stimulate the growth of new blood vessels.

Professor Peter Weissberg, of the British Heart Foundation which part-funded the study, said the finding was highly significant.

"This vital finding may pave the way for the development of a drug to knock out the molecule - or its effects.

"Such a treatment would have enormously beneficial effects on one of the most devastating and life-threatening complications of diabetes."

Dr Iain Frame, of the charity Diabetes UK, warned against drawing firm conclusions from animal experiments. But he added: "If this research is proven in humans, a treatment could be developed to remove the p75NTR protein from which many people with diabetes could benefit."

Diabetics are 15 times more likely to need a lower limb amputation than those without the disease.

About seven out of 10 people having an amputation will die within five years as a result of possible complications and their condition, figures suggest.


SEE ALSO
Diabetes
09 Feb 99 |  Medical notes

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