Willms B, Werner J, Holst J J, Orskov C, Creutzfeldt W, Nauck M A
Fachklinik für Diabetes und Stoffwechselkrankheiten, Bad Lauterberg, Germany.
J Clin Endocrinol Metab. 1996 Jan;81(1):327-32. doi: 10.1210/jcem.81.1.8550773.
The aim of the study was to investigate whether inhibition of gastric emptying of meals plays a role in the mechanism of the blood glucose-lowering action of glucagon-like peptide-1-(7-36) amide [GLP-1-(7-36) amide] in type 2 diabetes. Eight poorly controlled type 2 diabetic patients (age, 58 +/- 6 yr; body mass index, 30.0 +/- 5.2 kg/m2; hemoglobin A1c, 10.5 +/- 1.2%) were studied in the fasting state (plasma glucose, 11.1 +/- 1.1 mmol/L). A liquid meal of 400 mL containing 8% amino acids and 50 g sucrose (327 Kcal) was administered at time zero by a nasogastric tube. Gastric volume was determined by a dye dilution technique using phenol red. In randomized order, GLP-1-(7-36) amide (1.2 pmol/kg.min; Saxon Biochemicals) or placebo (0.9% NaCl with 1% human serum albumin) was infused between -30 and 240 min. In the control experiment, gastric emptying was completed within 120 min, and plasma glucose, insulin, C-peptide, GLP-1-(7-36) amide, and glucagon concentrations transiently increased. With exogenous GLP-1-(7-36) amide (plasma level, approximately 70 pmol/L), gastric volume remained constant over the period it was measured (120 min; P < 0.0001 vs. placebo), and plasma glucose fell to normal fasting values (5.4 +/- 0.7 mmol/L) within 3-4 h, whereas insulin was stimulated in most, but not all, patients, and glucagon remained at the basal level or was slightly suppressed. In conclusion, GLP-1-(7-36) amide inhibits gastric emptying in type 2 diabetic patients. Together with the stimulation of insulin and the inhibition of glucagon secretion, this effect probably contributes to the blood glucose-lowering action of GLP-1-(7-36) amide in type 2-diabetic patients when studied after meal ingestion. At the degree observed, inhibition of gastric emptying, however, must be overcome by tachyphylaxis, reduction in dose, or pharmacological interventions so as not to interfere with the therapeutic use of GLP-1-(7-36) amide in type 2 diabetic patients.
本研究旨在探讨抑制进餐时胃排空是否在胰高血糖素样肽-1-（7-36）酰胺[GLP-1-（7-36）酰胺]降低2型糖尿病患者血糖作用机制中发挥作用。对8例血糖控制不佳的2型糖尿病患者（年龄58±6岁；体重指数30.0±5.2kg/m²；糖化血红蛋白10.5±1.2%）在空腹状态（血浆葡萄糖11.1±1.1mmol/L）下进行研究。在时间零点经鼻胃管给予含8%氨基酸和50g蔗糖（327千卡）的400mL流食。采用酚红染料稀释技术测定胃容积。按随机顺序在-30至240分钟期间输注GLP-1-（7-36）酰胺（1.2pmol/kg·min；Saxon生化公司）或安慰剂（含1%人血清白蛋白的0.9%氯化钠）。在对照实验中，胃排空在120分钟内完成，血浆葡萄糖、胰岛素、C肽、GLP-1-（7-36）酰胺和胰高血糖素浓度短暂升高。给予外源性GLP-1-（7-36）酰胺（血浆水平约70pmol/L）后，在测量期间（120分钟）胃容积保持恒定（与安慰剂相比，P<0.0001），血浆葡萄糖在3-4小时内降至正常空腹值（5.4±0.7mmol/L），而大多数（但并非全部）患者的胰岛素受到刺激，胰高血糖素保持在基础水平或略有抑制。总之，GLP-1-（7-36）酰胺抑制2型糖尿病患者的胃排空。与刺激胰岛素和抑制胰高血糖素分泌一起，该作用可能在餐后研究时有助于GLP-1-（7-36）酰胺对2型糖尿病患者的降血糖作用。然而，在所观察的程度上，胃排空的抑制必须通过快速耐受、降低剂量或药物干预来克服，以免干扰GLP-1-（7-36）酰胺在2型糖尿病患者中的治疗应用。
