22 Feb 2017

Reversing damage caused by diabetes complications

L-R: Prof Karin Jandeleit-Dahm, Dr Stephen Gray and
Dr Jay Jha are researching inhibition of enzymes known
to cause kidney injury in diabetes. See
Diabetologia paper.
Life Scientist
By Eliza Watson

Diabetes affects around 1.7 million Australians. Sufferers with the disease are unable to control blood glucose levels either through failure to produce insulin (Type 1) or resistance of cells to insulin (Type 2). It can have a range of serious complications affecting the major arteries (macrovascular diseases) potentially leading to stroke, as well as causing kidney disease, nerve damage and loss of vision (microvascular diseases). The seriousness of these complications highlights the need for effective preventive measures.

In a collaborative study involving several Monash University researchers, a potential treatment was assessed and found to successfully reduce some of these complications.

Certain cell surface enzymes, known as NADPH oxidases or NOX, are thought to contribute to diabetic micro- and macrovascular diseases. Previous studies by this group have shown that an inhibitor of the NOX protein slowed down the development of kidney damage and plaque build-up in the arteries.

In the current study, the researchers assessed whether administration of the same NOX inhibitor could have the same beneficial effects on micro- and macrovascular diabetic complications once they had already progressed.

Using a diabetic mouse model with established diabetic vascular disease, the NOX inhibitor was administered at two different doses. The researchers found that renal (kidney) inflammation and fibrosis was lessened through a reduction in proinflammatory and profibrotic factors following administration of the inhibitor. Similarly, it was also found that some doses resulted in a reduction of aortic inflammation and aortic plaque. Moreover, they found that expression of specific NOX genes was decreased with certain doses of the inhibitor.

The researchers note that some of the effects seen were tissue and dose dependent and require further exploration.

This study highlights a potential treatment to relieve some vascular complications associated with diabetes. The results are particularly important as they have shown that the NOX inhibitor can help to attenuate or even reverse complications which have already progressed. As such, the results have formed the basis for clinical trials using the novel NOX1/4 inhibitor in diabetic nephropathy.

Through further research and understanding of the clinical effects of this inhibitor, this outcome may be helpful for the alleviation of established vascular disease in sufferers of diabetes.

Gray SP, Jha JC, Kennedy K, van Bommel E, Chew P, Szyndralewiez C, Touyz RM, Schmidt HH, Cooper ME, Jandeleit-Dahm KA. Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent reno- and atheroprotection even in established micro- and macrovascular disease. Diabetologia. 2017 Feb 3. doi: 10.1007/s00125-017-4215-5. [Epub ahead of print]

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