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New study turns established diabetic kidney disease theories on head

Washington, Oct 28 : While a prevailing theory suggests elevated cellular levels of glucose ultimately result in diabetic kidney disease, a new research led by Indian origin scientist has claimed that the truth may, in fact, be quite the opposite.


The findings by researchers at the University of California, San Diego School of Medicine could fundamentally change understanding of how diabetes-related diseases develop and how they might be better treated.

Current theory posits that impaired diabetic kidney function in humans as well as in mice is the result of chronically high glucose (sugar) levels which prompt energy-generating mitochondria in cells to produce an overabundance of superoxide anion - a highly reactive, toxic molecule that ultimately leads to downstream cellular damage, organ dysfunction and disease.

But Kumar Sharma, MD, professor of medicine and director of the Centre for Renal Translational Medicine (CRTM) at UC San Diego and colleagues upend this theory.

Rather than detecting higher-than-normal levels of superoxide in the damaged kidneys of the diabetic mice, the researchers discovered reduced superoxide production and suppressed mitochondrial activity.

When they stimulated the mitochondria by activating a key energy-sensing enzyme called AMPK, superoxide production increased but evidence of diabetic kidney disease markedly declined.

"Mitochondrial superoxide does not seem to be a causative factor of diabetic kidney disease. Indeed, when mitochondrial superoxide is increased with AMPK activation, there is reduced kidney disease, suggesting that improving mitochondrial function and superoxide production is actually beneficial for diabetic complications," Sharma said.

Sharma said the problematic reduction in AMPK activity is likely due to "caloric excess," which creates cellular imbalances associated with inflammation and fibrosis.

The study is published in Journal of Clinical Investigation.

--ANI (Posted on 28-10-2013)

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