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微囊化大鼠胰岛体外胰岛素释放动力学:微囊大小的影响

In vitro kinetics of insulin release by microencapsulated rat islets: effect of the size of the microcapsules.

作者信息

Chicheportiche D, Reach G

机构信息

Service de Diabétologie, Hôtel-Dieu, Paris, France.

出版信息

Diabetologia. 1988 Jan;31(1):54-7. doi: 10.1007/BF00279134.

DOI:10.1007/BF00279134
PMID:3280370
Abstract

Microencapsulation has been proposed to protect islets of Langerhans against immune rejection in xenogenic transplantation. However, to achieve glucose homeostasis in human diabetic patients, insulin release by microencapsulated islets must increase in response to a glucose load. We microencapsulated isolated rat islets using the alginate-polylysine procedure. Capsule size was found to range from 300 to 800 micron, and microencapsulated islets were separated according to their size. Groups of 10 microencapsulated islets, either small (350 micron) or large (650 micron) were placed in plastic microwells, in minimal Eagle's culture medium containing either 5.5 mol/l glucose (basal) or 16.5 mol/l glucose and 5.5 mol/l theophylline (stimulatory medium). The increase in insulin concentration in the surrounding medium was then serially determined over 30 min: (1) With the small capsules, insulin concentration rose from 199 +/- 20 to 297 +/- 58 microU/ml in basal medium, and from 236 +/- 23 to 510 +/- 121 microU/ml in stimulatory medium (n = 10 preparations), the difference between the data obtained with the basal or the stimulatory medium being significant (p less than 0.01) from the 5th min onwards. (2) With large capsules, insulin concentration increased from 182 +/- 9 to 266 +/- 44 microU/ml, and from 216 +/- 19 to 297 +/- 34 microU/ml in basal and stimulatory medium, respectively, with no apparent significant difference. The magnitude of insulin secretion in response to glucose by unencapsulated islets was, under similar conditions, seven-fold greater. We conclude therefore that the size of the microcapsules is an essential parameter which has to be considered for the optimisation of the microencapsulation procedure.

摘要

微囊化技术已被提出用于保护胰岛在异种移植中免受免疫排斥。然而,为了使人类糖尿病患者实现葡萄糖稳态,微囊化胰岛释放的胰岛素必须随着葡萄糖负荷的增加而增加。我们使用海藻酸盐-聚赖氨酸法对分离的大鼠胰岛进行了微囊化。发现胶囊大小在300至800微米之间,微囊化胰岛根据其大小进行了分离。将10个微囊化胰岛分为一组,小的(350微米)或大的(650微米),置于塑料微孔板中,在含有5.5摩尔/升葡萄糖(基础)或16.5摩尔/升葡萄糖和5.5摩尔/升茶碱的最低限度伊格尔培养基(刺激培养基)中。然后在30分钟内连续测定周围培养基中胰岛素浓度的增加:(1)对于小胶囊,基础培养基中胰岛素浓度从199±20微单位/毫升升至297±58微单位/毫升,刺激培养基中从236±23微单位/毫升升至510±121微单位/毫升(n = 10份制剂),从第5分钟起,基础培养基或刺激培养基获得的数据之间的差异具有显著性(p<0.01)。(2)对于大胶囊,基础培养基和刺激培养基中胰岛素浓度分别从182±9微单位/毫升增至266±44微单位/毫升和从216±19微单位/毫升增至297±34微单位/毫升,无明显显著差异。在类似条件下,未封装胰岛对葡萄糖的胰岛素分泌量要大7倍。因此,我们得出结论,微胶囊的大小是优化微囊化程序时必须考虑的一个重要参数。

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