IN 1906 extracts of mucosa from the upper small intestine from pigs were tested as a treatment of diabetes in the hope that “the internal secretion of the pancreas might be stimulated and initiated by the substance of the nature of a hormone yielded by the duodenal mucous membrane” (1). La Barre (2) introduced the name incretin for an unidentified substance that was thought to exert this effect. With the advent of insulin RIAs in the early 1960s (3), it was shown that insulin levels in the blood after ingestion of glucose were elevated out of proportion to the concentration of blood glucose when compared with the response to glucose given iv (4, 5). It was suggested that the potentiation of insulin secretion after oral glucose was mediated by a humoral substance which was released from the gut during glucose absorption and which stimulated insulin secretion (4, 5). Some years later a polypeptide was found (6, 7), which, due to its inhibitory effect on gastric acid secretion in dogs (8), was named gastric inhibitory polypeptide (GIP) (6, 7). Intravenous infusion of natural porcine GIP significantly enhanced serum immunoreactive insulin (IRI) and improved glucose tolerance after iv glucose in man (9). Later studies showed that GIP was insulinotropic only at glucose concentrations above 5.5–6.0 mmol/liter (10–12), and it was suggested that GIP should be renamed glucose-dependent insulinotropic polypeptide (13). There is, however, no general agreement to this new designation so the original name will be used throughout this review. Today GIP is considered to be the most important incretin factor (14–16), whereas the inhibitory effect of GIP on gastric acid secretion in normal subjects has been questioned (15).