title: GLP-2 and mesenteric blood flow.
abstract: The 33 amino acid peptide hormone GLP-2 is produced by enteroendocrine L-cells, the density of which is highest in the ileum and the colon, in response to the presence of nutrients in the lumen. The biological effect of GLP-2 is mediated by activation of a G-protein-coupled 7-transmembrane receptor. GLP-2 receptors are expressed in the brainstem, lungs, stomach, small intestine and colon, but not in the heart. It has been shown in several animal studies that GLP-2 infusion increases intestinal blood flow and that this increase is confined to the small intestine. The aim of the three studies, on which the thesis is based, was to investigate basic physiological effects of GLP-2, in healthy volunteers and in SBS patients, with focus on the effects on mesenteric blood flow, blood flow at other vascular sites and effects on cardiac parameters. These parameters have been evaluated after both meal stimulation and GLP-2 administration. The studies showed the following results: Blood flow: In all three studies, blood flow changes in the SMA after GLP-2 administration were similar regarding changes over time and degree of change. Blood flow changes were similar to changes seen after a standard meal. Only RI changes were registered in all three studies, but the TAMV changes in study 2 and 3 had similar characteristics. Cardiovascular parameters: In all three studies no significant changes in blood pressure were registered in relation to GLP-2 administration. In study two and three, where cardiac parameters also were registered by impedance cardiography, increases in CO and SV were seen. Plasma GLP-2: There were, as expected, supraphysiological GLP-2 plasma levels after SC administration. All three studies have shown rapid changes in mesenteric blood flow after administration GLP-2. The changes have been the same both in regards to time to maximum changes (increase) and relatively close in regards to maximum extent of change. The changes in the SBS patients were less than in the healthy test subjects. The findings leave no doubt about that GLP-2 is a potent regulator of upper splanchnic blood flow. The study findings also support the notion that the observed increased mesenteric blood flow, isolated to the SMA, is secondary to the metabolic responses to GLP-2, and that these are likely due to a paracrine action by GLP-2 acting on GLP-2R bearing cells such as enteric neurons, probably expressing NO. In conclusion GLP-2 increases mesenteric blood flow in healthy subjects and in SBS patients, the increase is equivalent to a standard meal and dose dependent. The blood flow is not increased at other arterial vascular sites. GLP-2 does not acutely alter blood pressure, but increases, probably as compensation, pulse rate and cardiac output. GLP-2 induced vascular response in the superior mesenteric artery is related with the length of remaining intestine in SBS patients. The effect is therefore likely to reflect the metabolic activity in the tissue rather than direct effect on the vascular system.
authors.affiliation: Department of Gastroenterology, Køge Hospital, Lykkebækvej 1, 4600 Køge, Denmark. lasssbremholm@dadlnet.dk
authors.forename: Lasse Bremholm
authors.initials: LB
authors.lastname: Hansen
mesh_terms: D017536:Carotid Artery, Common / Q000502:physiology; D002445:Celiac Artery / Q000502:physiology; D053767:Glucagon-Like Peptide 2 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D017538:Mesenteric Artery, Superior / Q000502:physiology*; D012077:Renal Artery / Q000502:physiology; D012778:Short Bowel Syndrome / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D053767:Glucagon-Like Peptide 2