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“Muscle Physiology and Metabolism” at DIfE

A new junior research group "Muscle Physiology and Metabolism" is headed by Dr. Maximilian Kleinert, who joined the DZD partner German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) at the beginning of the year. Over the next five years, he and his team will explore the molecular signaling pathways induced by physical activity that are involved in the regulation of glucose metabolism in skeletal muscle. This could help to develop new approaches for the prevention and treatment of type 2 diabetes.

Dr. Maximilian Kleinert. Source: DIfE/S. Ruprecht

 

Key role of skeletal muscle in glucose metabolism
Of all human organs, skeletal muscle is the largest organ that stores and utilizes glucose. Accounting for an average of about 40 percent of body weight in men and about 30 percent in women, skeletal muscle can store 300-500 grams of glucose in the form of glycogen. This is up to five times more glucose than the liver can store. "Thus, skeletal muscle plays a key role in glucose metabolism as a regulator of blood glucose homeostasis. Nevertheless, it is unfortunately still an underestimated organ in terms of possibilities for prevention and treatment of type 2 diabetes," said the 38-year-old scientist, who conducted research at the Institute for Diabetes and Obesity at Helmholtz Zentrum München from 2015 to 2020 and has been an assistant professor at the University of Copenhagen since 2019.

When the skeletal muscles have diminished capacity to absorb glucose despite high insulin and glucose concentrations in the blood, this is known as insulin resistance. This is considered a major risk factor for the development of type 2 diabetes.

Physical activity as a cornerstone in type 2 diabetes therapy
Exercise, like insulin, increases glucose uptake into muscle. However, there are differences between exercise-induced and insulin-induced glucose uptake in terms of molecular signaling pathways. Previous studies show that exercise-activated glucose uptake is maintained in insulin-resistant and diabetic skeletal muscle. This underscores why physical activity is considered a therapeutic cornerstone for people with type 2 diabetes.

In their studies, Maximilian Kleinert and his former research colleagues found that an intense training session on a bicycle led to about 1,000 altered protein phosphorylations in muscle, more than 90 percent of which had never been associated with exercise. "The currently known regulators of exercise-induced glucose uptake in muscle therefore only represent the tip of the iceberg," said Kleinert. He now wants to explore this approach further in a project funded by the German Research Foundation (DFG). To this end, he and his four-member junior research group team at DIfE are investigating a promising exercise-induced signaling protein in muscle. In order to identify and characterize this novel master regulator of skeletal muscle metabolism, the researchers are using novel mouse models and special investigation methods in muscle research.

"We are delighted that Maximilian Kleinert's promising project and outstanding expertise will strengthen our research on type 2 diabetes and obesity. His goal to understand more about the links between muscle metabolism, physical activity and the development of type 2 diabetes has great potential for translational research," said Professor Tilman Grune, scientific director at DIfE.

About Dr. Kleinert
Dr. Maximilian Kleinert became head of the junior research group Muscle Physiology and Metabolism at the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) in January 2021. His research focuses on the topics of energy and muscle metabolism as well as insulin resistance and exercise-induced insulin sensitivity.

A native of Berlin, Kleinert studied exercise physiology in the master’s degree program at the University of Texas in Austin (USA) from 2008 to 2010. During his subsequent doctoral studies at the University of Copenhagen in Denmark, Kleinert focused on insulin sensitivity and regulation of mTORC2, an important protein complex in glucose metabolism, in skeletal muscles.

In 2015, he accepted a position at Helmholtz Zentrum München – German Research Center for Environmental Health, where he became group leader of the Drug Development Unit in the Institute for Diabetes and Obesity in 2017. There his research focused on new combinatorial pharmacotherapies to improve the metabolic syndrome. In the meantime, he maintained his connection with the University of Copenhagen and has been an assistant professor there since 2019.