BLINDNESS, kidney failure and nerve damage caused by diabetes can be traced
to a single mechanism in cells, say researchers in New York. If drugs could be
found that target this mechanism, they say, these complications could be stopped
in their tracks.
Diabetes leads to hyperglycaemia鈥攅xcess glucose in the blood. This
damages nerves and the lining of blood vessels. When this happens in the retina,
for instance, it can cause blindness. 快猫短视频s already know of four major
biochemical pathways that give rise to this damage. 鈥淏ut there was nothing
connecting them,鈥� says Michael Brownlee of the Albert Einstein College of
Medicine in New York. So he and his colleagues set out to find the link.
Cells oxidise glucose to fuel their energy factories, or mitochondria. This
process involves a sequence of electron-transfer reactions called the
mitochondrial electron transport chain, which produces a free radical called
superoxide as a by-product.
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Normally, cells are able to dispose of the small amount of superoxide they
produce. But too much glucose in the blood upsets the cell鈥檚 delicate balance.
鈥淚f you push too many electrons through the mitochondrial electron transport
chain, it jams up. You start generating lots of superoxide,鈥� says Brownlee, who
presented his team鈥檚 findings at last week鈥檚 meeting in Jerusalem of the
European Association for the Study of Diabetes.
Brownlee and his team took cells from cows and humans genetically modified
them to produce high levels of a protein called UCP1, which indirectly reduces
levels of superoxide.
Significantly, stopping the build-up of superoxide blocked the four pathways
that lead to diabetic complications. 鈥淭hey are all connected because they are
downstream of one thing鈥攖he superoxide production,鈥� says Brownlee.
The electron transport chain may also explain a phenomenon called
hyperglycaemic memory, in which cells that have been exposed to excess glucose
later develop complications even after glucose concentrations have returned to
normal. Brownlee suggests that excess superoxide can cause mutations in
mitochondrial DNA. These mutations would in turn lead to more superoxide
production, he says.
鈥淭his is a really fundamental and highly important discovery,鈥� says Phillip
Gorden, former director of the National Institute of Diabetes and Digestive and
Kidney Diseases near Washington DC. 鈥淚t offers a lot of promise for therapies.鈥�