Drewes C, Nauck M A, Horn R, Holst J, Schmiegel W, Brabant G
Medizinische Universitätsklinik, Knappschafts-Krankenhaus, Bochum, Germany.
Acta Diabetol. 1997 Oct;34(3):230-4. doi: 10.1007/s005920050079.
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.
胰高血糖素样肽17-36酰胺和肥胖基因产物(瘦素)被认为参与进食的中枢调节。两者都可能从外周循环发挥作用以影响脑功能。为研究潜在的相互作用，将GLP-1([7-36酰胺]：分别为0.4、0.8 pmol kg-1 min-1或安慰剂)静脉输注(从-30至240分钟)给9名健康志愿者[年龄26±3岁，体重指数：22.9±1.6 kg/m2，糖化血红蛋白HbA1c：5.0%±0.2%(正常：4.0%-6.2%)，肌酐：1.1±0.1 mg/dl]，并(在0分钟时)通过鼻胃管给予液体试验餐(400 ml 8%氨基酸中含50 g蔗糖，总氨基酸80 g/l)。测定血浆瘦素(放射免疫测定法，RIA)、葡萄糖、胰岛素(微粒酶免疫测定法)、C肽(酶联免疫吸附测定法)和GLP-1(RIA)，并采用重复测量方差分析和学生t检验进行统计分析。基础状态下血浆瘦素浓度为31±6 pmol/l。进食后240分钟内以及对外源性GLP-1[7-36酰胺]输注均无变化(P = 0.99，实验与时间的交互作用)，导致GLP-1血浆平均水平分别为25±2和36±3(基础值6±1)pmol/l。另一方面，给予安慰剂后进食后葡萄糖(从基础值4.7±0.1 mmol/l在15分钟时升至6.0±0.2 mmol/l，P < 0.05)和胰岛素(从基础值28±2 pmol/l在45分钟时升至325±78 pmol/l，P < 0.05)明显升高。总之，(1)正常人类受试者进食液体混合餐后血浆瘦素水平无短期变化，(2)似乎不受血浆GLP-1[7-36酰胺]浓度的生理和药理升高的直接影响。这并不排除在脑(下丘脑)水平或更长时间尺度上的相互作用。
