Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance

Abstract

In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) (n=10) were compared with subjects with impaired glucose tolerance (IGT) (n=8). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower (P=0.031) and HSP90 was 380% higher (P<0.001) in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research.