A liquid mixed meal or exogenous glucagon-like peptide 1 (GLP-1) do not alter plasma leptin concentrations in healthy volunteers.

Glucagon-like peptide 1 [7-36 amide] (GLP-1) and the obese gene product (leptin) are thought to be involved in the central regulation of feeding. Both may act from the peripheral circulation to influence brain function. To study potential interactions, GLP-1 ([7-36 amide]: 0.4, 0.8 pmol kg-1 min-1 or placebo on separate occasions) was infused intravenously (from -30 to 240 min) into nine healthy volunteers [age 26 +/- 3 years, body mass index: 22.9 +/- 1.6 kg/m2, glycated haemoglobin HbA1c: 5.0% +/- 0.2% (normal: 4.0%-6.2%), creatinine: 1.1 +/- 0.1 mg/dl], and (at 0 min) a liquid test meal (50 g sucrose in 400 ml 8% amino acid, total amino acids 80 g/l) was administered via a nasogastric tube. Plasma leptin (radioimmunoassay, RIA), glucose, insulin (microparticle enzyme immunoassay), C-peptide (enzyme-linked immunosorbent assay) and GLP-1 (RIA) were measured, and statistical analysis was done with repeated-measures ANOVA and Student's t-test. Plasma leptin concentrations were 31 +/- 6 pmol/l in the basal state. They did not change within 240 min after meal ingestion nor in response to the infusion of exogenous GLP-1 [7-36 amide] (P = 0.99 for the interaction of experiment and time) leading to GLP-1 mean plasma levels of 25 +/- 2 and 36 +/- 3 (basal 6 +/- 1) pmol/l. On the other hand, glucose (from basal 4.7 +/- 0.1 to 6.0 +/- 0.2 mmol/l at 15 min, P < 0.05) and insulin (from basal 28 +/- 2 to 325 +/- 78 pmol/l at 45 min, P < 0.05) increased clearly after the meal with placebo. In conclusion, (1) plasma leptin levels in normal human subjects show no short-term changes after feeding a liquid mixed meal and (2) do not appear to be directly influenced by physiological and pharmacological elevations in plasma GLP-1 [7-36 amide] concentrations. This does not exclude interactions at the cerebral (hypothalamic) level or on more long-term temporal scales.