Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited by absorption of the nutrient. In other cases (e.g. lipid ingestion and digestion), stimulation may result from interaction with G-protein-coupled receptors expressed by the endocrine cells and activation of intracellular signals (cAMP, IP3, etc.). It is the rate at which these mechanisms are being activated that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses are relatively unchanged. Increased secretion of cholecystokinin, neurotensin, GLP-1 and PYY may contribute to the appetite inhibitory effect and, therefore, the weight loss after the operations. Indeed, in experiments in which the actions of PYY and GLP-1 were prevented, food intake increased by 20%. The increased insulin responses after the operation, one of the important mechanisms whereby these operations cause diabetes remission, is clearly due to a combination of the increased glucose absorption rates and the exaggerated GLP-1 secretion. The hormonal changes are therefore very important for the metabolic effects of the operations.