Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
J Clin Endocrinol Metab. 2011 Jun;96(6):1763-70. doi: 10.1210/jc.2010-2146. Epub 2011 Mar 16.
Our objective was to examine the mechanisms via which exenatide attenuates postprandial hyperglycemia in type 2 diabetes mellitus (T2DM).
Seventeen T2DM patients (44 yr; seven females, 10 males; body mass index = 33.6 kg/m(2); glycosylated hemoglobin = 7.9%) received a mixed meal followed for 6 h with double-tracer technique ([1-(14)C]glucose orally; [3-(3)H]glucose i.v.) before and after 2 wk of exenatide. In protocol II (n = 5), but not in protocol I (n = 12), exenatide was given in the morning of the repeat meal. Total and oral glucose appearance rates (RaT and RaO, respectively), endogenous glucose production (EGP), splanchnic glucose uptake (75 g - RaO), and hepatic insulin resistance (basal EGP × fasting plasma insulin) were determined.
After 2 wk of exenatide (protocol I), fasting plasma glucose decreased (from 10.2 to 7.6 mm) and mean postmeal plasma glucose decreased (from 13.2 to 11.3 mm) (P < 0.05); fasting and meal-stimulated plasma insulin and glucagon did not change significantly. After exenatide, basal EGP decreased (from 13.9 to 10.8 μmol/kg · min, P < 0.05), and hepatic insulin resistance declined (both P < 0.05). RaO, gastric emptying (acetaminophen area under the curve), and splanchnic glucose uptake did not change. In protocol II (exenatide given before repeat meal), fasting plasma glucose decreased (from 11.1 to 8.9 mm) and mean postmeal plasma glucose decreased (from 14.2 to 10.1 mm) (P < 0.05); fasting and meal-stimulated plasma insulin and glucagon did not change significantly. After exenatide, basal EGP decreased (from 13.4 to 10.7 μmol/kg · min, P = 0.05). RaT and RaO decreased markedly from 0-180 min after meal ingestion, consistent with exenatide's action to delay gastric emptying.
Exenatide improves 1) fasting hyperglycemia by reducing basal EGP and 2) postmeal hyperglycemia by reducing the appearance of oral glucose in the systemic circulation.
我们的目的是研究 exenatide 减轻 2 型糖尿病（T2DM）患者餐后高血糖的机制。
17 例 T2DM 患者（44 岁；7 名女性，10 名男性；体重指数 = 33.6 kg/m(2)；糖化血红蛋白 = 7.9%）接受混合餐，6 小时后用双示踪技术（口服[1-(14)C]葡萄糖；静脉内[3-(3)H]葡萄糖）。在方案 II（n = 5）中，但不在方案 I（n = 12）中，在重复进餐的早晨给予 exenatide。分别测定总葡萄糖和口服葡萄糖出现率（RaT 和 RaO）、内源性葡萄糖生成（EGP）、内脏葡萄糖摄取（75 g - RaO）和肝胰岛素抵抗（基础 EGP×空腹血浆胰岛素）。
exenatide 治疗 2 周后（方案 I），空腹血糖降低（从 10.2 降至 7.6 mmol/L），餐后平均血糖降低（从 13.2 降至 11.3 mmol/L）（P < 0.05）；空腹和餐刺激的血浆胰岛素和胰高血糖素没有显著变化。exenatide 后，基础 EGP 降低（从 13.9 降至 10.8 μmol/kg·min，P < 0.05），肝胰岛素抵抗降低（均 P < 0.05）。RaO、胃排空（对乙酰氨基酚曲线下面积）和内脏葡萄糖摄取没有变化。在方案 II（餐前给予 exenatide）中，空腹血糖降低（从 11.1 降至 8.9 mmol/L），餐后平均血糖降低（从 14.2 降至 10.1 mmol/L）（P < 0.05）；空腹和餐刺激的血浆胰岛素和胰高血糖素没有显著变化。exenatide 后，基础 EGP 降低（从 13.4 降至 10.7 μmol/kg·min，P = 0.05）。从进餐 0 至 180 分钟，RaT 和 RaO 显著降低，与 exenatide 延迟胃排空的作用一致。
exenatide 通过降低基础 EGP 改善 1）空腹高血糖，通过降低循环中口服葡萄糖的出现率改善 2）餐后高血糖。
