The incretin effect — almost magical

Abstract

The foundations for modern medical treatments for diabetes mellitus and obesity were laid more than 60 years ago by several scientific groups in London. Importantly, the 1965 publication of Intestinal factors in the control of insulin secretion by McIntyre and colleagues investigated both glucose metabolism and the role of the liver. This work contributed markedly to the discovery of the incretin effect in humans and to the identification of the incretin hormones.

In this simple and elegant study, McIntyre and colleagues describe a difference in both blood levels of glucose and insulin secretion for two glucose administration routes: intrajejunal infusion or intravenous infusion. The study involved nine healthy individuals and two patients with liver cirrhosis with vascular shunts from the portal vein to the vena cava (thereby bypassing the liver). For each administration method, four healthy individuals and one patient with a vascular shunt were given a rapid infusion with 10–20% glucose. The intrajejunally administered glucose was given over 10–20 minutes, whereas the same amount of glucose (50–60 g in total) was infused intravenously for 30–45 minutes to simulate the time needed for digestion and therefore compare the blood levels of glucose with the intrajejunal administration. In all five individuals, blood levels of glucose were 1.6-fold higher following the intravenous infusion than with the intrajejunal infusion, and, remarkably, insulin levels were 4.3-fold higher following the intrajejunal infusion than with the intravenous infusion, reflecting the presence of highly insulinotropic factors in the intestines.