外源性胰高血糖素样肽I（7-36）酰胺在I型糖尿病患者中的血糖稳定作用及空腹高血糖的降低

Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients.

作者信息

Creutzfeldt W O, Kleine N, Willms B, Orskov C, Holst J J, Nauck M A

机构信息

Department of Medicine, Georg-August-University, Göttingen, Germany.

出版信息

Diabetes Care. 1996 Jun;19(6):580-6. doi: 10.2337/diacare.19.6.580.

DOI:10.2337/diacare.19.6.580

PMID:8725855

Abstract

OBJECTIVE

Glucagon-like peptide I(7-36) amide (GLP-1) is a physiological incretin hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers glucagon concentrations, and thereby normalizes elevated fasting plasma glucose concentrations in type II diabetic patients. It is not known whether GLP-1 has effects also in fasting type I diabetic patients.

RESEARCH DESIGN AND METHODS

In 11 type I diabetic patients (HbA1c 9.1 +/- 2.1%; normal, 4.2-6.3%), fasting hyperglycemia was provoked by halving their usual evening NPH insulin dose. In random order on two occasions, 1.2 pmol . kg-1 . min-1 GLP-1 or placebo was infused intravenously in the morning (plasma glucose 13.7 +/- 0.9 mmol/l; plasma insulin 26 +/- 4 pmol/l). Glucose (glucose oxidase method), insulin, C-peptide, glucagon, GLP-1, cortisol, growth hormone (immunoassays), triglycerides, cholesterol, and nonesterified fatty acids (enzymatic tests) were measured.

RESULTS

Glucagon was reduced from approximately 8 to 4 pmol/l, and plasma glucose was lowered from 13.4 +/- 1.0 to 10.0 +/- 1.2 mmol/l with GLP-1 administration (plasma concentrations approximately 100 pmol, P < 0.0001), but not with placebo (14.2 +/- 0.7 to 13.2 +/- 1.0). Transiently, C-peptide was stimulated from basal 0.09 +/- 0.02 to 0.19 +/- 0.06 nmol/l by GLP-1 (P < 0.0001), but not by placebo (0.07 +/- 0.02 to 0.07 +/- 0.02). There was no significant effect on nonesterified fatty acids (P = 0.34), triglycerides (P = 0.57), cholesterol (P = 0.64), cortisol (P = 0.40), or growth hormone (P = 0.53).

CONCLUSIONS

Therefore, exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations. However, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients, in whom insulin secretion (C-peptide response) was stimulated 20-fold.

摘要

目的

胰高血糖素样肽I（7 - 36）酰胺（GLP - 1）是一种生理性肠促胰岛素激素，在略高于生理剂量时，可刺激胰岛素分泌，降低胰高血糖素浓度，从而使II型糖尿病患者升高的空腹血糖浓度恢复正常。目前尚不清楚GLP - 1对空腹的I型糖尿病患者是否也有作用。

研究设计与方法

在11例I型糖尿病患者中（糖化血红蛋白A1c为9.1±2.1%；正常范围为4.2 - 6.3%），通过将其通常的夜间中效胰岛素剂量减半来诱发空腹高血糖。在两个不同的时间，随机给予患者静脉输注1.2 pmol·kg⁻¹·min⁻¹的GLP - 1或安慰剂（上午输注，此时血浆葡萄糖浓度为13.7±0.9 mmol/l；血浆胰岛素浓度为26±4 pmol/l）。检测葡萄糖（葡萄糖氧化酶法）、胰岛素、C肽、胰高血糖素、GLP - 1、皮质醇、生长激素（免疫分析法）、甘油三酯、胆固醇和非酯化脂肪酸（酶法检测）。

结果

给予GLP - 1后，胰高血糖素从约8 pmol/l降至4 pmol/l，血浆葡萄糖从13.4±1.0 mmol/l降至10.0±1.2 mmol/l（血浆浓度约为100 pmol，P<0.0001），而给予安慰剂时无此变化（从14.2±0.7 mmol/l降至13.2±1.0 mmol/l）。GLP - 1可使C肽从基础值0.09±0.02 nmol/l短暂升高至0.19±0.06 nmol/l（P<0.0001），而安慰剂无此作用（从0.07±0.02 nmol/l升至0.07±0.02 nmol/l）。对非酯化脂肪酸（P = 0.34）、甘油三酯（P = 0.57）、胆固醇（P = 0.64）、皮质醇（P = 0.40）或生长激素（P = 0.53）无显著影响。