The researchers report evidence in people and mice, linking low adiponectin levels to insulin resistance and reductions in the number of "cellular power plants" called mitochondria in skeletal muscle. The findings suggest that therapies designed to boost the adiponectin signal might prove beneficial for the treatment of insulin resistance and diabetes, they said.
"We have discovered a skeletal muscle pathway by which adiponectin increases mitochondrial number and function and exerts antidiabetic effects," said lead author Anthony Civitarese from Pennington Biomedical Research Center in Baton Rouge, Louisiana.
Mitochondria utilize nutrient components, including fats and carbohydrates, to generate usable energy. The number of mitochondria therefore influences the way that muscles function. For example, people who exercise regularly have more mitochondria in their muscles than do those who are sedentary.
Earlier studies found that obese individuals and those with type 2 diabetes have reduced adiponectin concentrations, the researchers said. The new study examined the effects of that reduced adiponectin on skeletal muscle.
The researchers first examined children whose parents had type 2 diabetes and those with no family history of the disease. Muscle taken from individuals prone to diabetes was insulin resistant and had lower than normal concentrations of mitochondrial enzymes, suggesting some dysfunction, they found. The level of adiponectin also correlated with the estimated number of mitochondria in the muscle samples.
Further study of adiponectin-deficient mice similarly found that the animals were resistant to insulin and exhibited deficits in mitochondria in their skeletal muscles.
Finally, the researchers showed that adiponectin treatment of human muscle tissue in culture sparked the production of mitochondria. The treatment also limited the production of harmful free radicals, or reactive oxygen species, a sign that the mitochondria were operating more efficiently.
The current findings, together with earlier studies that showed that adiponectin increases glucose uptake from the blood stream, suggest that the hormone might have therapeutic potential for those with insulin resistance or type 2 diabetes, Civitarese said.
However, adiponectin itself is difficult to produce in the quantities that would be required for a drug, he added.
"It may be that a mimetic drug that acts like adiponectin might prove beneficial," he said.
The researchers include Anthony E. Civitarese, Barbara Ukropcova, Stacy Carling, Matthew Hulver, Eric Ravussin, and Steve R. Smith of the Pennington Biomedical Research Center in Baton Rouge, LA; Ralph A. DeFronzo of the University of Texas Health Science Center in San Antonio, TX; Lawrence Mandarino of the University of Texas Health Science Center in San Antonio, TX and Arizona State University in Tempe, AZ.
This study was supported partly by RO1 AG20478 (ER); DK04796 (LJM); DK066483 (LJM); M01RR001346 (LJM), DK24092 (RAD) and USDA20033432314010 (SRS).
Civitarese et al.: "Role of adiponectin in human skeletal muscle bioenergetics." Publishing in Cell Metabolism 4, 75–87, JULY 2006 DOI 10.1016/j.cmet.2006.05.002 www.cellmetabolism.org
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