The skeletal muscles of men and women process glucose and fat differently. A study by the University Hospital of Tübingen, the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich, and the German Center for Diabetes Research (DZD) provides the first comprehensive molecular analysis of these differences. Such peculiarities could explain why metabolic diseases such as diabetes manifest differently in women and men—and why they respond differently to exercise.
Skeletal muscles are far more than just "engines" for movement: they play a central role in glucose metabolism and thus also in the development of type 2 diabetes. Approximately 85 percent of insulin-dependent glucose uptake takes place in the muscles. This means that if muscle cells are less sensitive to insulin, for example in cases of insulin resistance, glucose is absorbed less efficiently from the blood. Exercise specifically counteracts this.
But how differently muscles work in women and men has long been underestimated. Researchers led by Simon Dreher and Cora Weigert have now investigated precisely this question. They examined muscle biopsies from 25 healthy, but overweight adults (16 women, 9 men) around the age of 30. The subjects had not previously participated in regular physical activity. For eight weeks, they completed one-hour endurance training sessions three times a week, consisting of 30 minutes of cycling and 30 minutes of walking on a treadmill.
Muscle samples were taken before the start, after the first training session, and at the end of the program. Using cutting-edge molecular biology techniques, including epigenome, transcriptome, and proteome analyses, the team investigated gender differences at various levels.
The result: Even the first training session triggered a stronger stress response in men at the molecular level, evident in the increased activation of stress genes and an increase in the muscle protein myoglobin in the blood. In addition, male muscles showed a pronounced pattern of so-called fast-twitch fibers, which are designed for short-term, intense exercise and preferentially use glucose as an energy source.
Women had significantly higher amounts of proteins, which are responsible for the uptake and storage of fatty acids: an indication of more efficient fat utilization. After eight weeks of regular endurance training, the muscles of both sexes adapted, and muscle fiber-specific differences decreased. At the same time, both women and men produced increased amounts of proteins that promote the utilization of glucose and fat in the mitochondria, the "powerhouses of the cells."
"These adaptations indicate an overall improved metabolic performance, which may help reduce the risk of type 2 diabetes," says Weigert. "Our new findings could help better predict individual diabetes risk in the future and better tailor exercise therapy recommendations for women and men."
What's next? The scientists now want to investigate the role that sex hormones such as estrogen and testosterone play in these differences – and how hormonal changes in old age influence the risk of metabolic diseases.
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