Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.
Diabetes. 2013 Aug;62(8):2752-6. doi: 10.2337/db13-0140. Epub 2013 Apr 1.
Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-(3)H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10(-4) dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10(-14) dL/kg/min(2) per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.
Exendin-(9,39) 是胰高血糖素样肽-1 (GLP-1) 受体的竞争性拮抗剂。然而，目前尚不清楚它是否具有自身独特的直接作用。我们假设 Exendin-(9,39) 和 GLP-1-(9,36)酰胺对健康受试者的激素分泌和β细胞功能以及葡萄糖代谢具有直接作用。含有 [3-(3)H]葡萄糖的葡萄糖被输注以模拟餐后全身葡萄糖的出现。在不同的日子里，以随机顺序输注盐水、GLP-1-(9,36)酰胺或 30 pmol/kg/min (Ex 30) 或 300 pmol/kg/min (Ex 300) 的 Exendin-(9,39)。整合后的葡萄糖浓度略有但显著升高 (365 ± 43 与 383 ± 35 与 492 ± 49 与 337 ± 50 mmol/6 h，盐水、Ex 30、Ex 300 和 GLP-1-[9,36]酰胺，分别；P = 0.05)。胰岛素分泌在各组之间没有差异。然而，Exendin-(9,39) 降低了胰岛素作用 (25 ± 4 与 20 ± 4 与 18 ± 3 与 21 ± 4 10(-4) dL/kg[min per μU/mL]；P = 0.02)，导致 Exendin-(9,39) 输注期间的处置指数 (DI) 降低 (1,118 ± 118 与 816 ± 83 与 725 ± 127 与 955 ± 166 10(-14) dL/kg/min(2) per pmol/L；P = 0.003)。各组间内源性葡萄糖生成和葡萄糖清除率无显著差异。我们得出结论，Exendin-(9,39)，而不是 GLP-1-(9,36)酰胺，可降低健康人群的胰岛素作用和 DI。
