ARS | Publication request: Resistance training alters cytokine gene expression in skeletal muscle of adults with type 2 diabetes

Submitted to: International Journal of Immunopathology and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 1, 2006
Publication Date: October 1, 2006
Publisher's URL: http://www.ncbi.nlm.nih.gov/sites/entrez
Citation: Gordon, P.L., Vannier, E., Hamada, K., Layne, J., Hurley, B.F., Roubenoff, R., Castaneda, C. 2006. Resistance training alters cytokine gene expression in skeletal muscle of adults with type 2 diabetes. International Journal of Immunopathology and Pharmacology. 19(4):739-749.

Interpretive Summary: Chronic inflammation due to activation of the innate immune system plays a key role in the development of insulin resistance and diabetes. Critical mediators of this process are the inflammatory cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6. In health, local inflammation is the protective response to tissue injury by which early release of inflammatory cytokines contributes to tissue regeneration. Whether the acute protective inflammatory response is impaired in states of chronic inflammation such as diabetes is poorly understood. Moreover, there are no reports on whether resistance training modulates cytokine expression in skeletal muscle of diabetics. The purpose of this study was to measure transcript levels for TNF-alpha, IL-1beta, TGF-beta1, and CD18, a pan-leukocyte surface marker, in the vastus lateralis muscle of individuals with poorly controlled type 2 diabetes prior to and following 16 weeks of either, resistance training plus usual diabetic care or usual diabetic care only (controls). Following the 16-wk intervention, resistance training elicited a 2.6-fold increase in IL-1beta transcript levels that was greater than the mean change observed in the control group. There was a significant overall time effect on TNF-alpha and TGF-beta1 levels as compared to controls, and these changes were associated with one another. Muscle hypertrophy and improved glycemic control was seen in the exercise group compared to controls. These data establish that resistance training alters the profile of cytokine gene expression in muscles of older adults with poorly controlled diabetes. It shows that resistance training in this population results in muscle hypertrophy and improved glycemic control, despite increased inflammatory cytokine expression in the trained muscle. Our study also shows for the first time that resistance training was accompanied by a greater transcription for TGF-beta1, a cytokine involved in tissue regeneration and remodeling. However, resistance training failed to reduce TNF-alpha transcript levels in subjects with diabetes. This finding is in sharp contrast with the observation that resistance training suppresses TNF-alpha gene expression in the muscle of healthy elders. Therefore, further investigation is necessary to determine whether resistance training selectively alters inflammatory cytokine expression in the muscle of individuals with type 2 diabetes.

Technical Abstract: Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes. Whether resistance training modulates inflammation in muscles of diabetic patients remains unknown. We examined the expression of genes encoding the cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and transforming growth factor-beta-1 (TGF-beta1) as well as the pan-leukocyte marker CD18. Thirty men and women (67 ± 7 years) were randomized to either 16 weeks of resistance training and usual diabetes care (EX) or to usual diabetes care only (CON). Muscle biopsies were obtained from the vastus lateralis muscle prior to the 16-week intervention, and 72 h following the maximal strength test post-intervention. Fiber cross-sectional area (CSA) was determined following ATPase staining. Cytokine and CD18 transcript levels were assessed by real-time PCR. Resistance training increased CSA of type I and II fibers (both P < 0.05) and IL-1beta transcript levels (P = 0.05). TNF-alpha (P < 0.05) and TGF-beta1 transcripts (P < 0.05) increased over time in the EX group, but these increases did not differ from those in the CON group. In both groups, the increase in CD18 transcripts remained minimal. The two groups differ by the relationship between changes in CD18 and changes in cytokine transcripts, suggesting that resistance training affects the source of cytokines in muscle. Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy, despite a greater accumulation of inflammatory cytokine transcripts in muscle.