The idea that the lack of an intestinal factor is responsible for some forms of diabetes mellitus was first expressed in a publication by Moore et al. in 1906.’They suggested that “the duodenum does yield a chemical excitant for the internal secretion of the pancreas”, by analogy with secretin controlling its exocrine secretion. Three possible disturbances of this mechanism in diabetes mellitus were discussed:(i)“nonsecretion of the excitant”;(ii) the inability of diabetic B cells to respond (“these cells are not capable of excitation”); and (iii)” changes in the oxidizing tissues such as the liver and muscle”. Their attempts to treat diabetes with duodenal extracts, however, remained inconclusive. Later, Zunz and LaBarre, 2 by analogy with excretin (the active principle of upper gut extracts stimulating pancreatic exocrine secretion) coined the term “incretin” for a component of small intestinal extracts that augmented pancreatic endocrine responses and lowered plasma glucose. At the same time, Heller was able to reduce postprandial hyperglycaemia with duodenal extract^.^ He called the active principle of these preparations duodenin. It was only when reliable measurements of plasma insulin concentrations were possible, after the development of radioimmunological assays: that the contribution of gut factors to insulin responses after glucose administration could be examined further. Plasma insulin increased more