Schirra J, Kuwert P, Wank U, Leicht P, Arnold R, Göke B, Katschinski M
Clinical Research Unit of Gastrointestinal Endocrinology, Philipps-University, Marburg, Germany.
Proc Assoc Am Physicians. 1997 Jan;109(1):84-97.
In this study of eight healthy male volunteers, we investigated the effects of graded doses of subcutaneous glucagon like peptide-1(7-36)amide (GLP-1) on: 1) the gastric emptying pattern of a mixed liquid meal (300 kcal); 2) pancreatic enzyme secretion; 3) antroduodenal motility; and 4) the glycemic response as well as releases of insulin, C-peptide, and glucagon. GLP-1, 0.125 nmol/kg, or 0.25 nmol/kg, or placebo was injected subcutaneously 5 min before meal ingestion. Subcutaneous GLP-1 dose-dependently prolonged the lag period (i.e., the time to reach maximal velocity of gastric emptying) by 46.2% (low dose) and 93.7% (high dose) (p < .05) but left unaltered maximal emptying velocity, total emptying time, and exponential emptying rate. With and without GLP-1, a fed motor pattern was induced by the meal and was terminated by an antral phase III when 98% of the meal had emptied. In parallel to the prolonged lag period, GLP-1 dose-dependently inhibited antral and duodenal motility and coordinated antroduodenal contractions by > 50% (low dose) and > 70% (high dose) (p < .05). GLP-1 initially reduced and thereafter transiently stimulated pancreatic enzyme secretion. This pattern correlated with the prolonged lag period and mirrored the delayed gastric emptying. GLP-1 retarded and diminished the postprandial glucose peak and reduced the total plasma glucose response by 46.6% (low dose) and by 59.4% (high dose) (p < .05). Both doses of GLP-1 delayed the postprandial insulin peak, enhanced total insulin release, and diminished postprandial responses of glucagon and pancreatic polypeptide. The duration of the lag period strongly correlated with the timing of postprandial glucose and insulin peaks (p < .001). The initial delay of gastric emptying, the enhancement of postprandial insulin release, and the inhibition of postprandial glucagon release were independent determinants (p < .01-.05) of the postprandial glucose response after subcutaneous administration of GLP-1.
在这项针对8名健康男性志愿者的研究中，我们调查了不同剂量皮下注射胰高血糖素样肽-1（7-36）酰胺（GLP-1）对以下方面的影响：1）混合液体餐（300千卡）的胃排空模式；2）胰腺酶分泌；3）胃十二指肠运动；4）血糖反应以及胰岛素、C肽和胰高血糖素的释放。在进餐前5分钟皮下注射0.125 nmol/kg、0.25 nmol/kg的GLP-1或安慰剂。皮下注射GLP-1剂量依赖性地使延迟期（即达到胃排空最大速度的时间）延长了46.2%（低剂量）和93.7%（高剂量）（p<0.05），但最大排空速度、总排空时间和指数排空率未改变。无论有无GLP-1，进餐均诱导出进食运动模式，并在98%的餐食排空时由胃窦III期终止。与延迟期延长并行，GLP-1剂量依赖性地抑制胃窦和十二指肠运动，并使胃十二指肠收缩协调性提高>50%（低剂量）和>70%（高剂量）（p<0.05）。GLP-1最初减少，随后短暂刺激胰腺酶分泌。这种模式与延迟期延长相关，并反映了胃排空延迟。GLP-1延迟并减弱了餐后血糖峰值，使血浆葡萄糖总反应降低了46.6%（低剂量）和59.4%（高剂量）（p<0.05）。两种剂量的GLP-1均延迟了餐后胰岛素峰值，增强了胰岛素总释放，并减弱了胰高血糖素和胰多肽的餐后反应。延迟期的持续时间与餐后血糖和胰岛素峰值的时间密切相关（p<0.001）。皮下注射GLP-1后，胃排空的初始延迟、餐后胰岛素释放的增强以及餐后胰高血糖素释放的抑制是餐后血糖反应的独立决定因素（p<0.01-0.05）。
