Mechanisms of cold-induced improvements in glucose homeostasis

Cold exposure has proven itself as a potential novel therapy to improve skeletal muscle glucose uptake and glucose homeostasis in T2DM patients, although the underlying mechanisms remain unknown. In this thesis, two hypothesis were investigated underlying these improvements: 1) activation of adrenergic receptors (which are involved in the so-called fight or flight response) and 2) shivering during cold exposure. First of all, it was demonstrated that activation of a specific adrenergic receptor, the β2-adrenergic receptor, could stimulate skeletal muscle glucose uptake in obese mice. Treatment with a specific compound able to activate this receptor could also improve their glucose homeostasis. This research was thereafter translated to the clinical and it was shown that treatment with this compound could also improve skeletal muscle glucose uptake in healthy young males. Secondly, it was investigated whether shivering at 10 degrees Celsius (1 hour/day) could improve glucose homeostasis in overweight/obese individuals. In line with the hypothesis, shivering for 1h/day improved glucose homeostasis, although the underlying mechanisms remained unknown. All in all, it was shown that both methods could potentially be used as a novel therapy for T2DM.