胰高血糖素样肽-1（7-36）酰胺对正常受试者和糖尿病患者的抗糖尿病作用。

Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus.

作者信息

Gutniak M, Orskov C, Holst J J, Ahrén B, Efendic S

机构信息

Department of Endocrinology, Karolinska Institute, Stockholm, Sweden.

出版信息

N Engl J Med. 1992 May 14;326(20):1316-22. doi: 10.1056/NEJM199205143262003.

DOI:10.1056/NEJM199205143262003

PMID:1348845

Abstract

BACKGROUND

Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of insulin in physiologic concentrations. Its effects in patients with diabetes mellitus are not known.

METHODS

We compared the effect of an infusion of GLIP that raised plasma concentrations of GLIP twofold with the effect of an infusion of saline, on the meal-related release of insulin, glucagon, and somatostatin in eight normal subjects, nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM), and eight patients with insulin-dependent diabetes mellitus (IDDM). The blood glucose concentrations in the patients with diabetes were controlled by a closed-loop insulin-infusion system (artificial pancreas) during the infusion of each agent, allowing measurement of the meal-related requirement for exogenous insulin. In the patients with IDDM, normoglycemic-clamp studies were performed during the infusions of GLIP and saline to determine the effect of GLIP on insulin sensitivity.

RESULTS

In the normal subjects, the infusion of GLIP significantly lowered the meal-related increases in the blood glucose concentration (P less than 0.01) and the plasma concentrations of insulin and glucagon (P less than 0.05 for both comparisons). The insulinogenic index (the ratio of insulin to glucose) increased almost 10-fold, indicating that GLIP had an insulinotropic effect. In the patients with NIDDM, the infusion of GLIP reduced the mean (+/- SE) calculated isoglycemic meal-related requirement for insulin from 17.4 +/- 2.8 to 2.0 +/- 0.5 U (P less than 0.001), so that the integrated area under the curve for plasma free insulin was decreased (P less than 0.05) in spite of the stimulation of insulin release. In the patients with IDDM, the GLIP infusion decreased the calculated isoglycemic meal-related insulin requirement from 9.4 +/- 1.5 to 4.7 +/- 1.4 U. The peptide decreased glucagon and somatostatin release in both groups of patients. In the normoglycemic-clamp studies in the patients with IDDM, the GLIP infusion significantly increased glucose utilization (saline vs. GLIP, 7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg per kilogram of body weight per minute; P less than 0.01).

CONCLUSIONS

GLIP has an antidiabetogenic effect, and it may therefore be useful in the treatment of patients with NIDDM:

摘要

背景

胰高血糖素样肽-1（7-36）酰胺（胰高血糖素样促胰岛素肽，或GLIP）是一种胃肠肽，在生理浓度下可增强胰岛素的释放。其对糖尿病患者的作用尚不清楚。

方法

我们比较了使血浆GLIP浓度升高两倍的GLIP输注与生理盐水输注对8名正常受试者、9名非胰岛素依赖型糖尿病（NIDDM）肥胖患者和8名胰岛素依赖型糖尿病（IDDM）患者进餐相关的胰岛素、胰高血糖素和生长抑素释放的影响。在输注每种药物期间，糖尿病患者的血糖浓度通过闭环胰岛素输注系统（人工胰腺）进行控制，从而能够测量进餐相关的外源性胰岛素需求量。在IDDM患者中，在输注GLIP和生理盐水期间进行正常血糖钳夹研究，以确定GLIP对胰岛素敏感性的影响。

结果

在正常受试者中，输注GLIP可显著降低进餐相关的血糖浓度升高（P<0.01）以及胰岛素和胰高血糖素的血浆浓度（两项比较P均<0.05）。胰岛素生成指数（胰岛素与葡萄糖的比值）增加了近10倍，表明GLIP具有促胰岛素作用。在NIDDM患者中，输注GLIP使计算得出的等血糖进餐相关胰岛素需求量从17.4±2.8单位降至2.0±0.5单位（P<0.001），因此尽管刺激了胰岛素释放，但血浆游离胰岛素曲线下的积分面积仍减小（P<0.05）。在IDDM患者中，GLIP输注使计算得出的等血糖进餐相关胰岛素需求量从9.4±1.5单位降至4.7±1.4单位。该肽在两组患者中均降低了胰高血糖素和生长抑素的释放。在IDDM患者的正常血糖钳夹研究中，GLIP输注显著增加了葡萄糖利用率（生理盐水组与GLIP组分别为7.2±0.5与8.6±0.4毫克/千克体重/分钟；P<0.01）。