THE presence of intestinal factors regulating the function of endocrine secretion from the pancreas was first described in 1906 by Moore and colleagues (1). The idea that humoral factors secreted from the gut might act in this way arose after the recognition of “secretin” as a regulator of pancreatic secretion. Later it became evident that the hypoglycemic intestinal factor(s) is/are not “secretin” and the names “incretin” and “duodenin” were introduced in the 1920s and 1930s to describe these putative mediators (2–4). For several decades the nature of this/these factor(s) remained largely unknown (5–8) and before the first incretin hormone was chemically characterized, several other hormones produced in the gastrointestinal tract were discovered.

The connection between the gastrointestinal tract and the endocrine pancreas was shown in the 1960s when insulin became measurable in plasma. In these classic studies, the insulin response to oral glucose and intravenous glucose, resulting in nearly identical plasma glucose levels, was compared (9–11). A much higher insulin secretion was found after oral glucose. It was calculated that up to 50% of the insulin release after oral glucose is triggered by the “entero-insular-axis,” a term introduced in 1969 (12).