In Germany there is the humorous saying "Sport ist Mord" (Exercise kills!), which is commonly used as an excuse not to exercise. Yet physical activity improves blood glucose regulation and protects against type 2 diabetes. Exercise and muscle contraction, as well as the body's own insulin, cause an increased uptake of glucose from the blood into the muscle cells. This leads to a sustained reduction in the blood glucose level – especially after a meal.
However, in people with type 2 diabetes, the insulin action is impaired and blood glucose levels are elevated. Impaired glucose uptake by the muscles is therefore considered an early indicator of diabetes and can be detected even before the onset of clinical symptoms. While the hormone insulin, which is produced in the pancreas, can only inadequately lower blood glucose in type 2 diabetes – commonly referred to as insulin resistance – the lowering effect of muscle contraction in people with diabetes is largely normal. People with type 2 diabetes can therefore lower their blood glucose levels and counteract the progression of the disease to a certain extent through targeted physical activity. Exactly how muscle activity and insulin cause glucose uptake into the cells has so far not been adequately studied. Scientists from the German Diabetes Center (DDZ) have now focused on this research area and discovered a novel mechanism that explains how insulin and muscle contraction work together.
The Institute of Clinical Biochemistry and Pathobiochemistry at the DDZ, under the supervision of Professor Hadi Al-Hasani and Dr. Alexandra Chadt, investigated those muscle cells that exhibited limited insulin action. The chosen experimental model, which was also developed at the DDZ, involves the silencing of several important genes required for insulin signal transduction and glucose uptake into the cell. "In the process, we found an alternative signaling pathway that can be used to activate glucose uptake in muscle even in the presence of insulin resistance and type 2 diabetes. Apparently, muscle cells contain several signaling pathways that are required for the uptake of glucose from the blood," said Dr. Chadt, deputy head of the Pathobiochemistry group. The findings may prove highly relevant for diabetes therapy in the future. The DDZ is already conducting intensive research in the area of exercise and its influence on diabetes in its in-house fitness studio for study participants.
"This signaling pathway, which we refer to as AMPK/Rac1, represents a kind of natural reserve mechanism and could be exploited for the development of novel agents for the treatment of insulin resistance and diabetes," said Professor Al-Hasani, director of the Institute of Clinical Biochemistry and Pathobiochemistry at the DDZ. "The role of this mechanism in the development of different subtypes of diabetes, especially when there is little improvement in blood glucose from regular exercise, should be further investigated in future studies."
Wendt, C., Espelage, L., Eickelschulte, S., Springer, C., Toska, L., Scheel, A., Bedou, A. D., Benninghoff, T., Cames, S., Stermann, T., Chadt, A., Al-Hasani, H. Contraction-mediated glucose transport in skeletal muscle is regulated by a framework of AMPK, TBC1D1/4 and Rac1. Diabetes 2021, DOI: https://doi.org/10.2337/db21-0587