Dietary glucose is a preferred source of energy, but it remains unknown how the mammalian brain rapidly detects and discriminates this sugar from other sweeteners, and whether this depends on nutritional environment and metabolic need. Our results show that signals generated by metabolism-dependent and -independent actions of oral glucose can each be recruited to guide nutrient choice. Further, glucose (or its non-metabolizable analog) evokes a discernible pattern of neural activity from calorie-matched fructose in the central gustatory system, and this is conditioned by diet. Although the brain responses and corresponding consummatory behaviors do not require sweet taste receptor input, the results indicate that the sweet receptor is important for integrating nutritional states with metabolic pathways in the taste system and ultimately guiding intake towards glucose-yielding substrates.