Vella A, Shah P, Basu R, Basu A, Camilleri M, Schwenk F W, Holst J J, Rizza R A
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Diabetes. 2001 Mar;50(3):565-72. doi: 10.2337/diabetes.50.3.565.
In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at approximately 5.5 mmo/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [3H]glucose) was infused via an intraduodenal tube at a rate of 20 micromol.kg(-1).min(-1). Insulin concentrations were increased to approximately 500 pmol/l while glucose was clamped at approximately 8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-2H2]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P = 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 +/- 1.5 vs. 4.8 +/- 0.8 micromol.kg(-1).min(-1)). On the other hand, flux through the hepatic uridine-diphosphate- glucose pool did not differ between study days (14.2 +/- 5.5 vs. 13.0 +/- 4.2 micromol.kg(-1).min(-1)), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 +/- 2.9 vs. 1.3 +/- 1.4 micromol.kg(-1).min(-1)), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 +/- 10.0 vs. 69.3 +/- 6.3 micromol.kg(-1).min(-1); P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes.
体外研究表明，胰高血糖素样肽-1(7-36)-酰胺（GLP-1）可增强肝脏对葡萄糖的摄取。为了确定GLP-1是否会增加人体内脏对葡萄糖的摄取，我们对7名1型糖尿病患者进行了两次研究。在这两次研究中，夜间通过可变胰岛素输注将血糖维持在约5.5 mmol/L。在研究当天上午，开始输注生长抑素、胰高血糖素和生长激素以维持基础激素水平。通过十二指肠内导管以20 μmol·kg⁻¹·min⁻¹的速率输注葡萄糖（含[³H]葡萄糖）。在接下来的4小时内，通过用[6,6-²H₂]葡萄糖标记的可变静脉葡萄糖输注将胰岛素浓度提高到约500 pmol/L，同时将血糖钳制在约8.8 mmol/L。令人惊讶的是，在输注GLP-1期间，十二指肠内输注葡萄糖的全身出现率高于输注生理盐水期间（P = 0.01），表明初始内脏葡萄糖摄取率较低（P < 0.05）（1.4±1.5对4.8±0.8 μmol·kg⁻¹·min⁻¹）。另一方面，研究日之间通过肝脏尿苷二磷酸葡萄糖池的通量没有差异（14.2±5.5对13.0±4.2 μmol·kg⁻¹·min⁻¹），这意味着糖原合成速率相当。GLP-1还损害了（P < 0.05）胰岛素诱导的内源性葡萄糖生成抑制（6.9±2.9对1.3±1.4 μmol·kg⁻¹·min⁻¹），但导致葡萄糖消失呈时间依赖性增加（P < 口.01）（93.7±10.0对69.3±6.3 μmol·kg⁻¹·min⁻¹；P < 0.01），这仅在研究的最后一小时才明显。我们得出结论，在存在高血糖、高胰岛素血症和肠道给予葡萄糖的情况下，GLP-1会增加1型糖尿病患者的全身葡萄糖摄取，但不会增加内脏葡萄糖摄取。
