Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual β-cell function.
Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual β-cell function.
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作者：
Kielgast U;Holst JJ;Madsbad S
目的 研究外源性和内源性胰高血糖素样肽 1 (GLP-1) 对餐后血糖波动的影响，并表征具有或不具有残余 β 细胞功能的 1 型糖尿病患者肠促胰岛素激素的分泌。对 8 名具有 (T1D+) 的 1 型糖尿病患者、8 名无 (T1D−) 残余 β 细胞功能的 1 型糖尿病患者和 8 名健康匹配的对照受试者进行了研究，他们在混合膳食中同时输注 GLP-1 (1.2 pmol/kg/min)、盐水或 exendin 9-39 (300 pmol/kg/min)。餐前注射普通速效胰岛素一半剂量。测量血浆葡萄糖 (PG)、胰高血糖素、C 肽、总 GLP-1、完整葡萄糖依赖性促胰岛素多肽 (GIP)、游离脂肪酸、甘油三酯和血浆对乙酰氨基酚测得的胃排空率 (GE)。患者和对照受试者之间的肠促胰岛素反应没有差异。输注 GLP-1 可使两组 1 型糖尿病患者的峰值 PG 降低 45%。在 T1D+ 患者中，餐后 PG 降至空腹水平以下，并且与输注生理盐水的对照受试者没有区别。在 T1D− 患者中，餐后 PG 保持在空腹水平。 GLP-1输注降低了所有组中的GE和胰高血糖素水平，并增加了T1D+患者和对照受试者的空腹C肽。阻断内源性 GLP-1 受体的作用会增加所有组中的内源性 GLP-1 分泌，并增加 T1D+ 和 T1D− 患者的餐后血糖、胰高血糖素和 GE。在阻断内源性 GLP-1 受体作用期间，T1D+ 患者的胰岛素生成指数（胰岛素与葡萄糖的比率）下降。 1 型糖尿病患者对膳食的肠促胰素反应正常。在 1 型糖尿病患者中，无论残余的 β 细胞功能如何，外源性 GLP-1 都能将餐后血糖峰值降低 45%。内源性 GLP-1 通过调节胰高血糖素水平、GE 和 β 细胞对葡萄糖的反应来调节餐后血糖波动。 GLP-1 对 1 型糖尿病患者的长期影响应在未来的临床试验中进行研究。
To investigate the effect of exogenous as well as endogenous glucagon-like peptide 1 (GLP-1) on postprandial glucose excursions and to characterize the secretion of incretin hormones in type 1 diabetic patients with and without residual β-cell function. Eight type 1 diabetic patients with (T1D+), eight without (T1D−) residual β-cell function, and eight healthy matched control subjects were studied during a mixed meal with concomitant infusion of GLP-1 (1.2 pmol/kg/min), saline, or exendin 9-39 (300 pmol/kg/min). Before the meal, half dose of usual fast-acting insulin was injected. Plasma glucose (PG), glucagon, C-peptide, total GLP-1, intact glucose-dependent insulinotropic polypeptide (GIP), free fatty acids, triglycerides, and gastric emptying rate (GE) by plasma acetaminophen were measured. Incretin responses did not differ between patients and control subjects. Infusion of GLP-1 decreased peak PG by 45% in both groups of type 1 diabetic patients. In T1D+ patients, postprandial PG decreased below fasting levels and was indistinguishable from control subjects infused with saline. In T1D− patients, postprandial PG remained at fasting levels. GLP-1 infusion reduced GE and glucagon levels in all groups and increased fasting C-peptide in T1D+ patients and control subjects. Blocking endogenous GLP-1 receptor action increased endogenous GLP-1 secretion in all groups and increased postprandial glucose, glucagon, and GE in T1D+ and T1D− patients. The insulinogenic index (the ratio of insulin to glucose) decreased in T1D+ patients during blockade of endogenous GLP-1 receptor action. Type 1 diabetic patients have normal incretin responses to meals. In type 1 diabetic patients, exogenous GLP-1 decreases peak postprandial glucose by 45% regardless of residual β-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and β-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.
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影响因子：
3.3
作者：
Kielgast, Urd;Holst, Jens J.;Madsbad, Sten
通讯作者：
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影响因子：
7.7
作者：
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影响因子：
8.2
作者：
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影响因子：
4.8
作者：
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通讯作者：
Perfetti, R
影响因子：
--
作者：
MADSBAD, S;ALBERTI, KGMM;REGEUR, L
通讯作者：
REGEUR, L