title: Important species differences regarding lymph contribution to gut hormone responses.
abstract: BACKGROUND
  GLP-1 is secreted from the gut upon nutrient intake and stimulates insulin secretion. The lymph draining the intestine may transport high levels of GLP-1 to the systemic circulation before it is metabolized by DPP-4. The aims of this study were to investigate to what extent the lymphatic system might contribute to the final level(s) of systemic circulating intact GLP-1 and, in addition, whether secretory profiles in intestinal lymph might reflect lamina propria levels of GLP-1 i.e. before capillary uptake and degradation by endothelial dipeptidyl peptidase-4 (DPP-4).
  
  
  METHODS
  7 pigs of the YDL-strain were catheterized in the portal vein, carotid artery and cisterna chyli (lymph). Neuromedin C (NC) was infused through an ear vein catheter, before and after injection of a selective DPP-4 inhibitor (vildagliptin). Total and intact GLP-1 levels were measured throughout the 150min experiments using specific sandwich ELISAs. DPP-4 activity was measured spectrophotometrically.
  
  
  RESULTS
  Concentrations of both total and intact GLP-1 were markedly lower in lymph compared to plasma samples, and did not increase significantly in response to stimulation with NC in the absence/presence of vildagliptin. In contrast, total and intact GLP-1 levels increased significantly in the portal vein and carotid artery. DPP-4 activity was lower in lymph than plasma, and was reduced further by vildagliptin.
  
  
  CONCLUSIONS
  Our observations indicate that the lymphatic system does not transport high levels of intact GLP-1 to the systemic circulation, and that GLP-1 levels in cisternal lymph do not reflect the hormone levels in the intestinal lamina propria.
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: mariehansendk@gmail.com.
authors.forename: Marie
authors.initials: M
authors.lastname: Hansen
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: KRJs@novonordisk.com.
authors.forename: Karina R
authors.initials: KR
authors.lastname: Hjøllund
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: bhartmann@sund.ku.dk.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: astridp@sund.ku.dk.
authors.forename: Astrid
authors.initials: A
authors.lastname: Plamboeck
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: deacon@sund.ku.dk.
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: hgk795@ku.dk.
authors.forename: Nicolai J
authors.initials: NJ
authors.lastname: Wewer Albrechtsen
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Section for Translational Metabolism, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: jjholst@sund.ku.dk.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D013045:Species Specificity; D013552:Swine; D000077597:Vildagliptin
chemical_list: D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane
keywords: DPP-4; GLP-1; Lamina propria; Lymph; Neuromedin C; Portal vein