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Metformin reverses PKD
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ResearchItaly

Metformin reverses PKD

25.03.2013 - Italian researchers have tracked down the signalling pathway causing
polycystic kidney disease and identified a promising target.

Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases, affecting an estimated 12.5 million people worldwide. Due
to multiple fluid-filled cysts, both kidneys enlarge and can also damage
liver, pancreas and - more rarely - heart and brain. Currently no treatment exists for the autosomally and recessively inherited forms of PKD.

The PKD-1 gene is mutated in 85% of the autosomal dominant form. Italian researchers have now found that the disorder can be targeted by an existing diabetes drug in combination with a glucose analogon. The team headed by Alessandra Boletta from San Raffaele Institute in Milan found that the PKD-1 mutation caused a switch in sugar metabolism towards aerobic glycolysis due to the inactivation of the master regulator AMPK (liver kinase B1-AMP activated protein kinase).

Forced activation of AMPK either by rapamycin, the diabetes medicine metformin or the non-metabolised sugar analogon 2-deoxy-glucose (2-DG) triggered reduction of the number of cysts in a mouse model. AMPK activation revitalized the ERK signalling pathway which re-activated mTORC1 that in turn normalised glycolysis. The researchers believe that a combination therapy of 2-DG and metformin offers a treatment opportunity for the progressive disease.

© eurobiotechnews.eu/tg

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