Print“The new insights relating to the benefits of mitochondrial superoxide production, termed ‘mitochondrial hormesis,’ has raised many new exciting questions on the mechanisms linking mitochondrial superoxide production to beneficial effects, says Sharma.. ”
The use of anti-oxidants may be ineffective or even contribute to kidney disease and other complications of diabetes, rather than helping to treat such health problems, says Kumar Sharma, scientific founder of the biotech startup ClinMet. He presented that conclusion, based on growing unexpected findings that stimulating mitochondrial function and superoxide production results in improved markers of renal, cardiovascular and nerve dysfunction, at the recent meeting of the American Diabetes Association in San Diego.
“Scientists have long hypothesized that oxidative stress underlies diabetic complications and is driven by mitochondrial superoxide production and subsequent free radical damage to proteins and DNA,” says Sharma, who is also head of the Center for Renal Translational Medicine’s division of Nephrology-Hypertension, and the Institute of Metabolomic Medicine at UC San Diego. “However, clinical trials to date have failed to demonstrate a benefit for anti-oxidant approaches and in some cases, such anti-oxidants have even increased mortality.”
Sharma noted that data from multiple independent investigations, including clinical metabolomics studies, now suggest that in response to excess calories, mitochondrial activity is actually reduced in target tissues for diabetes complications, and such persistent reduction may lead to the release of pro-inflammatory and pro-fibrotic cytokines and subsequent organ dysfunction. “Approaches that restore mitochondrial function and mitochondrial superoxide production through exercise, caloric restriction, and medications should help promote tissue healing,” Sharma says.
New research measuring real-time superoxide production demonstrated that stimulating such production was linked to improvement in diabetic kidney disease. In independent studies in humans, it has also been shown that pretreatment of subjects with anti-oxidants, such as vitamin C and vitamin E, prior to exercise led to a loss in the protective benefit of exercise for insulin resistance.
“The new insights relating to the benefits of mitochondrial superoxide production, termed ‘mitochondrial hormesis,’ has raised many new exciting questions on the mechanisms linking mitochondrial superoxide production to beneficial effects,” Sharma says. “One potential link is that mitochondrial superoxide stimulates the master energy sensor AMPK, which when activated can suppress inflammation and fibrosis. The new theory is also a major boost for drugs that target and support mitochondrial function as potential treatments for diabetic complications and perhaps many other chronic diseases.”
Sharma’s company, ClinMet, aims to make the drug development process faster and more efficient by utilizing its proprietary urine metabolomics biomarker platform to provide drugmakers with clinically relevant insights and actionable information about drug efficacy, safety, and mechanism of action for molecules targeting diabetes, kidney disease, obesity, and cardiovascular disease.
June 15, 2014
http://www.burrillreport.com/article-new_theory_of_origin_of_diabetic_complications_.html
