title: GLP-1 released to the mesenteric lymph duct in mice: effects of glucose and fat.
abstract: Using a newly developed in vivo model measuring glucagon-like peptide-1 (GLP-1) in gut lymphatics in mice, we quantified GLP-1 secretion in vivo after glucose versus fat ingestion with and without concomitant DPP-4 inhibition. The mesenteric lymphatic duct was cannulated in anesthetized C57BL6/J mice and lymph was collected in 30 min intervals. Glucose or fat emulsion (Intralipid®) (0.03, 0.1 or 0.3 kcal) with or without DPP-4-inhibition (NVP DPP728; 10 μmol/kg) was administered by gastric gavage. Basal intact GLP-1 levels were 0.37±0.04 pmol/l (n=61) in lymph compared to 0.07±0.03 in plasma (n=6; P=0.04) and basal DPP-4 activity was 4.7±0.3 pmol/min/μl in lymph (n=23) compared to 22.3±0.9 pmol/min/μl in plasma (n=8; P<0.001). Lymph flow increased from 1.2±0.1 μl/min to 2.3±02μl/min at 30 min after glucose and fat administration, with no difference between type of challenge or dose (n=81). Lymph GLP-1 levels increased calorie-dependently after both glucose and fat but with different time courses in that glucose induced a transient increase which had returned to baseline after 90 min whereas the lipid induced a sustained increase which was still elevated above baseline after 210 min. Lymph GLP-1 appearance during 210 min was two to three-fold higher after glucose (7.4±2.3 fmol at 0.3 kcal) than after isocaloric fat (2.9±0.8 fmol at 0.3 kcal; P<0.001). The slope between caloric load and lymph GLP-1 appearance was, however, identical after glucose and fat. We conclude that lymph GLP-1 is higher than plasma GLP-1 whereas lymph DPP-4 activity is lower than plasma DPP-4 activity and that both glucose and fat clearly stimulate GLP-1 secretion calorie-dependently in vivo but with different time courses.
authors.affiliation: Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Ohlsson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Alison B
authors.initials: AB
authors.lastname: Kohan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.affiliation: Department of Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: Bo.Ahren@med.lu.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D005947:Glucose
keywords: DPP-4 inhibition; Fat; GLP-1; Glucose; Incretin secretion; Lymph