In 1906, it was first identified that the pancreas could be stimulated by factors from the gut to aid in removal of nutrients, and porcine small intestinal extract was used to treat diabetic patients (Graaf et al. 2016). In 1928, it was demonstrated that injection of secretin extracted from the small intestinal mucosa displays a hypoglycemic effect that is mediated through the pancreas (Creutzfeldt 2005). In the 1960s, it was shown that orally administered glucose induces a much stronger insulin response than that induced by intravenously administered glucose, despite the similar resulting plasma glucose levels – this was termed the “incretin effect” (Creutzfeldt 2005; Graaf et al. 2016). Gastric inhibitory peptide (GIP) was the first incretin hormone to be discovered in 1975, which is produced by K cells of the small intestine (Creutzfeldt 2005). It was then observed in 1981...
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