Introduction
type 2 diabetes mellitus (T2DM)Despite, insulin-stimulated skeletal muscle glucose, Reduced skeletal muscle glucose, femoral artery blood flow
Reduced skeletal muscle glucose uptake in response to insulin is central to the development of type 2 diabetes mellitus (T2DM)Despite the mounting evidence that βGiven these promising preclinical findings, we here investigated in a double-blinded, randomized, placebo-controlled, cross-over study whether clenbuterol treatment (2 × 20 µg/day for 14 days) could improve insulin-stimulated skeletal muscle glucose disposal in healthy, lean males, as assessed by the gold standard, two-step hyperinsulinemic-euglycemic clamp technique. To assess putative underlying physiological and molecular mechanisms, we performed in-depth metabolic phenotyping after clenbuterol treatment using state-of-the-art techniques. Thus, we determined body composition, assessed (sleeping) energy metabolism by whole-room calorimetry, femoral artery blood flow velocity using Doppler ultrasonography whereas muscle biopsies were taken in the overnight fasted state to test if clenbuterol treatment was associated with enhanced skeletal muscle mTORC2 activation and GLUT4 translocation.Here, we show that clenbuterol treatment increases insulin-stimulated peripheral glucose uptake and non-oxidative glucose disposal (NOGD) in healthy young males by ~13 and ~18%, respectively. However, these effects occurred independent of changes in skeletal muscle GLUT4 translocation or mTORC2 activation. These results highlight the potential therapeutic value of targeting the β