PRESERVED INCRETIN ACTIVITY OF GLUCAGON-LIKE PEPTIDE-1 [7-36 AMIDE] BUT NOT OF SYNTHETIC HUMAN GASTRIC-INHIBITORY POLYPEPTIDE IN PATIENTS WITH TYPE-2 DIABETES-MELLITUS
PRESERVED INCRETIN ACTIVITY OF GLUCAGON-LIKE PEPTIDE-1 [7-36 AMIDE] BUT NOT OF SYNTHETIC HUMAN GASTRIC-INHIBITORY POLYPEPTIDE IN PATIENTS WITH TYPE-2 DIABETES-MELLITUS
复制标题
DOI：
10.1172/jci116186
复制
发表时间：
1993-01-01
影响因子：
15.9
通讯作者：
CREUTZFELDT, W
中科院分区：
文献类型：
--
作者：
NAUCK, MA;HEIMESAAT, MM;CREUTZFELDT, W
在2型糖尿病中，肠促胰岛素的总体作用降低。本研究旨在比较外源性肠促胰岛素激素（抑胃肽[GIP]和胰高血糖素样肽1 [GLP-1] 17-36酰胺]）在9例2型糖尿病患者（空腹血糖7.8 mmol/L;血红蛋白A1 c 6.3+/-0.6%）和9例年龄和体重匹配的正常受试者中的促胰岛素作用。合成人GIP（0.8和2.4 pmol/kg。min，每次1 h）、GLP-117 -36酰胺]（0.4和1.2 pmol/kg .在单独的实验中，在高血糖钳夹条件下（8.75 mmol/L）给予安慰剂。血浆GIP和GLP-117 -36酰胺]浓度（放射免疫测定法）与口服葡萄糖后的浓度相当，并且具有低输注速率，并且具有明显的超生理性。在两组中，GIP和GLP-117 -36酰胺]均剂量依赖性地增加胰岛素分泌（胰岛素，C-肽）（P < 0.05）。GIP治疗2型糖尿病患者的最大效应显著低于正常人（54%; P < 0.05）。使用GLP-1 [7-36酰胺]的2型糖尿病患者达到正常受试者C肽增量的71%（差异不显著）。在正常受试者中，在高血糖钳夹期间胰高血糖素降低，但在2型糖尿病患者中不降低，并且在两组中进一步通过GLP-1 [7-36酰胺]降低（P < 0.05），但不通过GIP。总之，在轻度2型糖尿病中，与GIP相反，GLP-117 -36酰胺保留了其大部分促胰岛素活性。它还降低胰高血糖素浓度。
In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] 17-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3+/-0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg . min over 1 h each), GLP-1 17-36 amide] (0.4 and 1.2 pmol/kg . min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 17-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 17-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 17-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.