Journal
REGULATORY PEPTIDES
Volume 189, Issue -, Pages 40-45Publisher
ELSEVIER
DOI: 10.1016/j.regpep.2014.02.001
Keywords
Lymph; Incretin secretion; DPP-4 inhibition; Glucose; Fat; GLP-1
Categories
Funding
- Swedish Medical Research Council
- Faculty of Medicine at the Lund University
- Region Skane
- Albert Pahlsson Foundation
- NIH [DK 59630, DK 92138, DK 76928, F32-091173-01]
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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(R)) (0.03, 0.1 or 0.3 kcal) with or without DPP-4-inhibition (NVP DPP728; 10 mu mol/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/mu l in lymph (n = 23) compared to 22.3 +/- 0.9 pmol/min/mu l in plasma (n = 8; P < 0.001). Lymph flow increased from 1.2 +/- 0.1 mu l/min to 2.3 +/- 02 mu l/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 03 kcal) than after isocaloric fat (2.9 +/- 0.8 fmol at 03 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. (C) 2014 Elsevier B.V. All rights reserved.
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