Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans

Background & Aims: Glucagon-like peptide 2(1-33) (GLP-2(1-33)), intestinally derived hormone, stimulates growth in rodent small and large bowel. To explore the physiology of GLP-2(1-33) secretion, we measured plasma GLP-2 levels in 6 healthy male volunteers, before and after test meals. Methods: Blood samples were collected over 24 hours with the subjects consuming a normal, solid mixed diet (2500 kcal) and for 4 hours after liquid test meals (400 kcal/300 mL) composed of carbohydrate, fat, or protein. All studies commenced at 9 AM. Plasma was extracted and analyzed in radioimmunoassays for N-terminal immunoreactive GLP-2 (N-IR-GLP-2; measures bioactive GLP-2(1-33)) as well as total IR-GLP-2 (T-IR-GLP-2), which includes GLP-2(1-33), GLP-2(1-33) (an inactive degradation product of GLP-2(1-33)), and the pancreatic major proglucagon fragment tan inactive precursor that contains GLP-2). Basal and nutrient-stimulated plasma samples were also analyzed by high-performance liquid chromatography to determine the levels of GLP-2(1-33) and GLP-2(3-33). Results: N-IR-GLP-2 levels were increased 2.0 +/- 0.2- to 2.8 +/- 0.5-fold 40 minutes after each mixed meal (P < 0.05-0.01) and returned to basal overnight, whereas T-IR-GLP-2 levels were increased 1.3 +/- 0.1-fold 40 minutes after breakfast only (P < 0.05). After ingestion of carbohydrate or fat alone, plasma N-IR-GLP-2 concentrations increased by 5.6 +/- 2.0- and 2.7 +/- 0.6-fold within 1 hour (P < 0.05). High-performance liquid chromatography analysis showed a relative increase in the levels of GLP-2(1-33) compared with GLP-2(3-33) (P < 0.05). Ingestion of the protein meal did not alter N-IR-GLP-2 levels, whereas T-IR-GLP-2 was increased by fat and protein (by 1.7 +/- 0.2-fold for each, P < 0.01) but not by carbohydrate. Conclusions: These results show that secretion of GLP-2(1-33) from the intestine is regulated in a nutrient-dependent manner in normal humans.