Understanding how male and female muscle metabolism influences diabetes risk

Recent research from the University Hospital of Tübingen, together with the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich and the German Center for Diabetes Research (DZD), sheds new light on the metabolic differences between male and female muscles. This comprehensive molecular study, published in Molecular Metabolism, offers insights into why diabetes and related metabolic disorders may manifest differently in women and men, and how they respond to physical activity.

Muscles are vital beyond enabling movement—they play a central role in glucose and fat metabolism. Approximately 85% of insulin-dependent glucose uptake occurs in skeletal muscles, making them a key factor in the development of type 2 diabetes. When muscle cells become less sensitive to insulin, a condition known as insulin resistance, glucose absorption from the bloodstream is impaired, increasing diabetes risk. Physical activity is known to counteract these effects, improving muscle sensitivity.

The study involved 25 healthy but overweight adults (16 women and 9 men) around 30 years of age, who had not previously engaged in regular exercise. Over eight weeks, participants completed thrice-weekly endurance training, alternating cycling and treadmill walking for 30 minutes each session. Muscle biopsies were performed at baseline, after the first training session, and at the end of the program. Using advanced molecular techniques—including epigenome, transcriptome, and proteome analyses—researchers examined sex-specific differences at various biological levels.

Key findings revealed that men exhibit a more pronounced molecular stress response immediately after exercise, characterized by increased activation of stress genes and higher levels of myoglobin, a muscle protein, in the blood. Additionally, male muscles tended to have more fast-twitch fibers, which are specialized for short bursts of intense activity and primarily utilize glucose for energy. In contrast, female muscles showed a higher abundance of proteins involved in absorbing and storing fatty acids, indicating a more efficient use of fats.

After eight weeks of training, these differences diminished as both sexes' muscles showed an increase in proteins that facilitate the utilization of glucose and fats within mitochondria, the energy-producing parts of cells. These adaptations suggest an overall enhancement in metabolic function, which could lower the risk of developing type 2 diabetes. According to researcher Cora Weigert, these findings may lead to improved prediction of individual diabetes risk and more personalized exercise recommendations based on sex.

Looking ahead, scientists aim to explore the influence of sex hormones like estrogen and testosterone on these metabolic differences, and how aging-related hormonal changes might impact metabolic disease susceptibility. This research underscores the importance of considering sex-specific biology in strategies to prevent and manage metabolic disorders.