Photo Credit: Jacob Wackerhausen

The following is a summary of “Acute Exercise Increases GDF15 and Unfolded Protein Response/Integrated Stress Response in Muscle in Type 2 Diabetes,” published in the July 2024 issue of Endocrinology by Sabaratnam, et al.

Regular exercise is a crucial strategy for preventing obesity and type 2 diabetes (T2D). Exerkines, which are molecules secreted in response to exercise or recovery, may play a role in improving systemic metabolism. Conversely, an impaired exerkine response to exercise and recovery could contribute to the development of cardiometabolic diseases. 

For a study, researchers sought to investigate whether the exercise-induced regulation of the exerkine growth differentiation factor 15 (GDF15) and its putative upstream regulators associated with the unfolded protein response (UPR) and integrated stress response (ISR) is impaired in skeletal muscle in patients with T2D compared to weight-matched, glucose-tolerant men.

In the study, 13 male patients with T2D and 14 age- and weight-matched overweight/obese glucose-tolerant men performed exercise at 70% of VO_2max for 1 hour. Blood and skeletal muscle biopsies were collected before exercise, immediately after exercise, and 3 hours into the recovery period. Serum and muscle transcript levels of GDF15 and key markers of UPR/ISR were measured, and the protein levels and phosphorylation of key UPR/ISR regulators were analyzed.

Acute exercise led to an increase in muscle gene expression and serum levels of GDF15 in both the T2D and control groups. During the recovery phase, muscle expression of GDF15 decreased towards baseline levels, while serum GDF15 levels remained elevated. Both groups exhibited increased expression of UPR/ISR markers, including ATF4, CHOP, EIF2K3 (encoding PERK), and PPP1R15A (encoding GADD34), with only CHOP remaining elevated 3 hours into recovery. Downstream molecules of the UPR/ISR, including XBP1-U, XBP1-S, and EDEM1, were increased following exercise and 3 hours into recovery in both groups. 

The phosphorylation levels of eIF2α-Ser51, a marker of both UPR and ISR, increased immediately after exercise in the control group but decreased 3 hours into recovery in both groups.

The study concluded that the exercise-induced regulation of GDF15 and key UPR/ISR markers is not impaired in patients with T2D compared to weight-matched glucose-tolerant controls. Both groups showed similar responses in these biomarkers in response to exercise and during recovery.

Reference: academic.oup.com/jcem/article-abstract/109/7/1754/7577592