Rate of Cellular Energy Production Lower in Persons at Risk for Type 2 Diabetes
The rate of insulin-stimulated energy production is significantly reduced in the muscles of lean, healthy young adults who have already developed insulin resistance and are at increased risk of developing diabetes later in life, according to a Yale School of Medicine study.
The new research by Gerald Shulman, M.D., professor of internal medicine, endocrinology, and senior author of the study, indicates that a decreased ability to burn sugars and fats efficiently is an early and central part of the diabetes problem. The new data also suggest that the basic defect lies within the mitochondria, which are the energy factories inside cells that produce most of the chemical power needed to sustain life.
The young adults studied by the research team are the offspring of parents who have type 2 diabetes, adding support to the idea that the risk can be inherited and that the problem begins well before diabetes symptoms become evident. The researchers observed that the mitochondria in the subjects’ muscle cells responded poorly to insulin stimulation. Normal mitochondria react to insulin by boosting production of an energy-carrying molecule, ATP, by 90 percent. But the mitochondria from the insulin-resistant people they tested only boosted ATP production by five percent.
Among their findings was also evidence for a severe reduction in the amount of insulin stimulated phosphorus transport into the muscle cells of the insulin-resistant participants. This also points to a dramatic defect in insulin signaling and may explain the observed abnormalities in insulin-stimulated power production in the insulin-resistant study subjects. Phosphorus is a key element in the mithochondrion’s complex energy-production process.
The co-authors were Kitt Petersen and Sylvie Dufour.
PLoS Medicine 2: www.plosmedicine.org (September 2005)