The effects of fasting and cold exposure on glucose uptake in skeletal muscles (tibialis anterior, quadriceps, and soleus), heart, and brown adipose tissue (BAT) were studied in conscious rats. Glucose uptake was estimated by determining the glucose metabolic index of individual tissues using the 2-[3H]deoxyglucose method. Fasting for 18 h at 25 degrees C decreased plasma glucose levels (-40%) and glucose uptake in heart (-95%) and skeletal muscles (-64-90%) but did not significantly affect glucose uptake in BAT. Fasting for 48 h did not further decrease these parameters. On the other hand, cold exposure (48 h at 5 degrees C) of fed animals did not alter plasma glucose levels but increased glucose uptake in heart (73%), skeletal muscles (126-326%), and particularly in BAT (95-fold). Remarkably, cold exposure stimulated glucose uptake in BAT and skeletal muscles of 18-h fasted rats by the same order of magnitude as in fed animals (percentagewise), thereby indicating that glucose represents an essential metabolite for shivering (muscles) and nonshivering (BAT) thermogeneses. In the heart of starved animals, the cold-induced increase in glucose uptake was even more important (8-fold) than in fed animals. Considering that cold exposure of fasted rats results in a severe insulinopenia, it is suggested that cold exposure stimulates glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways.