Glucagon-like peptide 2^1-33 (GLP-2^1-33), an 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.

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-2^3-33 (an inactive degradation product of GLP-2^1-33), and the pancreatic major proglucagon fragment (an 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.

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.

These results show that secretion of GLP-2^1-33 from the intestine is regulated in a nutrient-dependent manner in normal humans. GASTROENTEROLOGY 1999;117:99-105