Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, Hellerup, Denmark.
Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1038-46. doi: 10.1152/ajpendo.00665.2010. Epub 2011 Mar 8.
Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of glucagon during the first 30 min of the IIGI (day B) were observed. The glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a glucagon response in the midrange between the glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase glucagon secretion.
2 型糖尿病（T2DM）患者在口服葡萄糖耐量试验（OGTT）期间胰高血糖素抑制作用减弱，而等血糖静脉葡萄糖输注（IIGI）可使这些患者的胰高血糖素抑制作用正常。我们研究了肠激素葡萄糖依赖性胰岛素释放肽（GIP）、胰高血糖素样肽-1（GLP-1）和胰高血糖素样肽-2（GLP-2）在这种差异中的作用。在 10 例 T2DM 患者（年龄（均值±SE），51±3 岁；体重指数，33±2 kg/m²；HbA1c，6.5±0.2%）中，在 3 小时 50 g OGTT（第 A 天）和 IIGI（第 B 天）期间测量胰高血糖素反应。在另外 4 次 IIGI 期间，静脉输注 GIP（第 C 天）、GLP-1（第 D 天）、GLP-2（第 E 天）和三种激素的组合（第 F 天）。所有 6 天的研究均保持等血糖。正如预期的那样，OGTT 的初始阶段没有抑制胰高血糖素，而在 IIGI 的前 30 分钟观察到明显（P<0.05）更低的胰高血糖素水平。IIGI+GIP+GLP-1+GLP-2 输注期间的胰高血糖素反应与 OGTT 时不适当的胰高血糖素反应相等（P=无显著差异）。单独输注 GIP（第 C 天）引起胰高血糖素明显分泌过多，而 GLP-1 输注（第 D 天）导致 IIGI 期间胰高血糖素抑制作用增强。IIGI+GLP-2 输注（第 E 天）导致胰高血糖素反应处于 OGTT 和 IIGI 之间的中间范围。我们的结果表明，肠激素 GIP、GLP-1 和 GLP-2 可能在 T2DM 患者口服摄入葡萄糖时不适当的胰高血糖素反应中发挥作用，尤其是 GIP，可增加胰高血糖素分泌。
