瑞格列奈通过增加脉冲量急性增强脉冲式胰岛素分泌，而对脉冲频率无影响。

Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency.

作者信息

Juhl C B, Pørksen N, Hollingdal M, Sturis J, Pincus S, Veldhuis J D, Dejgaard A, Schmitz O

机构信息

Department of Medicine M (Endocrinology & Diabetes), Arhus Kommunehospital, University Hospital of Arhus, Denmark.

出版信息

Diabetes Care. 2000 May;23(5):675-81. doi: 10.2337/diacare.23.5.675.

DOI:10.2337/diacare.23.5.675

PMID:10834429

Abstract

OBJECTIVE

Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series.

RESEARCH DESIGN AND METHODS

We examined 8 healthy lean male subjects in a single-dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn).

RESULTS

Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 +/- 3.6 vs. 33.5 +/- 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 +/- 2.2 vs. 19.6 +/- 2.8 pmol x l(-1) x pulse(-1), P = 0.02) and amplitude (6.1 +/- 0.9 vs. 7.7 +/- 1.2 pmol x l(-1) x min(-1), P = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 +/- 0.3 vs. 3.2 +/- 0.4 pmol x l(-1) x min(-1), p = 0.06), while the interpulse interval was unaltered (6.8 +/- 1.0 vs. 5.4 +/- 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 +/- 0.045 vs. 0.670 +/- 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release.

CONCLUSIONS

In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.

摘要

目的

瑞格列奈是一种新型口服降糖药，作为餐时血糖调节剂，通过刺激胰岛素分泌来治疗2型糖尿病。本研究的目的是通过高频胰岛素采样和胰岛素浓度时间序列分析，探讨瑞格列奈对快速脉冲式胰岛素释放的作用。

研究设计与方法

我们采用单剂量双盲安慰剂对照交叉设计，对8名健康瘦男性受试者进行了研究。受试者过夜禁食后，开始采血，每分钟采集一次，持续120分钟。40分钟后，给予单剂量（0.5毫克）瑞格列奈或安慰剂。通过去卷积分析评估血清胰岛素浓度时间序列，并通过近似熵（ApEn）评估规律性统计量。

结果

服用瑞格列奈后，平均胰岛素浓度升高（基础期与刺激期，P值为安慰剂与瑞格列奈）（25.1±3.6对33.5±4.1皮摩尔/升，P<0.001）。服用瑞格列奈后，胰岛素分泌爆发量（15.8±2.2对19.6±2.8皮摩尔·升⁻¹·脉冲⁻¹，P = 0.02）和幅度（6.1±0.9对7.7±1.2皮摩尔·升⁻¹·分钟⁻¹，P = 0.008）增加。观察到基础胰岛素分泌有伴随增加的趋势（2.5±0.3对3.2±0.4皮摩尔·升⁻¹·分钟⁻¹，p = 0.06），而脉冲间期未改变（6.8±1.0对5.4±0.4分钟/脉冲，P = 0.38）。服用瑞格列奈后，ApEn显著增加（0.623±0.045对0.670±0.034，P = 0.04），表明胰岛素释放的振荡模式不太有序。