Glucagon-like peptide-2 increases mesenteric blood flow in humans

Abstract

Objective: Mesenteric blood flow is believed to be influenced by digestion and absorption of ingested macronutrients. We hypothesized that the intestinotrophic hormone, GLP-2 (glucagons-like peptide 2), may be involved in the regulation of mesenteric blood flow. Changes in mesenteric blood flow were measured by Doppler ultrasound scanning of the superior mesenteric artery (SMA). The aim of the study was to demonstrate the influence of GLP-2 on this flow, expressed as changes in resistance index (RI).

Material and methods: A homogeneous group of 10 fasting healthy volunteers completed a 2-day trial. On day 1, a standard meal was given, and RI measured in the SMA. On day 2, GLP-2 was infused intravenously (IV) at rates of 0.5, 1.0 and 2.0 pmol/kg/min over 3 x 45 min separated by a 15-20 min rest period. After a further 15-20 min of rest, 450 nmol synthetic GLP-2 was given subcutaneously (SC). RI in the SMA was measured before, during and after the meal and GLP-2 infusions.

Results: After IV infusion of GLP-2, the following decreases in RI were observed: 0.5 pmol/kg/min: 2.7% (range 0-6.3%), 1.0 pmol/kg/min: 6.7% (range 0.4-15.9%), 2.0 pmol/kg/min: 15.3% (range 9.6-22.7%) p<0.00802. When given SC, GLP-2 elicited a maximum average change in RI of 15.6% (range 5.0-28.1%). The standard meal elicited a 14.7% (range 8.8-21.6%) change, p<0.020 There was a similar change in RI over time (0-90 min) after a standard meal and after subcutaneous GLP-2, p<0.005.

Conclusions: Our study showed a significant association between IV and SC administration of synthetic GLP-2 and changes in mesenteric blood flow. An exponential dose-response relationship was observed after IV infusion. The meal-induced changes in mesenteric blood flow over time were similar to those obtained by SC GLP-2. Thus, our results support the hypothesis that GLP-2 is an important regulator of mesenteric blood flow.