Variation in response to exercise in type 2 diabetes associated to VEGFA and PGC1-α expression
Henrik Wagner1, Helene Fischer2, Marie Degerblad1, Peter Båvenholm3, Suad Efendic1 & Thomas Gustafsson2
Objective: The individual changes in insulin sensitivity in response to exercise demonstrate a large variation. The mechanisms contributing to improved insulin sensitivity by training in type 2 diabetes are not fully known but presumably involve both metabolic and structural adaptations. The present study investigates if associations exist between changes in expression of key genes and improved insulin sensitivity, VO2max and glycemic control following exercise training in type 2 diabetes.
Methods: Nineteen subjects with type 2 diabetes were randomized to a 12 week intervention with structured exercise. Nine of the subjects were also randomized to acarbose treatment. Hyperinsulinemic euglycemic clamp, maximal exercise test and HbA1c were performed before and after the intervention. Muscle biopsies were obtained in resting state for quantification of mRNA-expression. Statistical analyses of relative change in gene expression were performed by multiple linear regression with sex, acarbose treatment and relative changes in insulin sensitivity, VO2max and HbA1c as independent variables. All subjects gave informed consent to study participation and the protocol was approved by an Independent Ethics Committee.
Results: Sixteen subjects (4 females and 12 males) completed the study per protocol and were included in the analyses. Change in VEGFA expression was positively associated to an increase in insulin sensitivity (P=0.003) and to a decrease in HbA1c (P=0.02). Change in VEGFA receptor 1 expression was also positively correlated with an increase in insulin sensitivity (P=0.03) and a decrease in HbA1c (P=0.007). An increase in PGC1-α expression showed a significant association with an improvement of insulin sensitivity (P=0.05).
Conclusions: In this study, the variation in physical adaptation to exercise in type 2 diabetes was associated to relative changes in VEGFA and PGC1-α expression in muscle. The difference in training induced expression of these factors could participate in the known variation in the exercise training generated changes in insulin sensitivity.