The remarkable control of diabetes by the gastric bypass remains to be explained. Although it may be totally due to the weight loss Induced by the operation, it is likely that the detour of the hormonally active foregut plays a role as well. This keynote address explores the pathophysiology of non-insulin-dependent diabetes mellitus and reviews the data which support the thesis that the gastric antrum, duodenum, and proximal jejunum modulate glucose metabolism and insulin action.