Accumulation of topically applied porcine insulin in the retina and optic nerve in normal and diabetic rats.
Accumulation of topically applied porcine insulin in the retina and optic nerve in normal and diabetic rats.
复制标题
局部应用的猪胰岛素在正常和糖尿病大鼠的视网膜和视神经中的积累。
DOI：
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复制
发表时间：
2002
影响因子：
4.4
通讯作者：
S. Lake
中科院分区：
文献类型：
--
作者：
S. Koevary;J. Nussey;S. Lake
目的
探讨局部注射胰岛素与视网膜和视神经潴留的药代动力学关系。
方法
将胰岛素滴眼液（约15微升：0.75%猪胰岛素+0.5%渗透促进剂）应用于正常和糖尿病大鼠的眼睛。在16小时内以不同的间隔处死大鼠，并在ELISA中分析双眼视网膜和视神经中胰岛素的存在。通过检查静脉注射胰岛素对视网膜胰岛素水平的影响以及通过检查断头大鼠中滴眼液给药的影响，探讨了全身吸收胰岛素对视网膜中胰岛素发现的影响程度。
结果
正常大鼠视网膜胰岛素水平在滴眼液后20分钟显著升高并达到峰值（0.7pg/μ g; P < 0.00001）。糖尿病视网膜中的水平在60分钟时达到峰值（0.66 pg/microg; P < 0.004），并且比正常大鼠在更长的时间内保持升高。正常和糖尿病大鼠对侧视网膜显示较少量胰岛素的延迟积累。正常大鼠和糖尿病大鼠的视神经中也出现显著升高，正常大鼠在20分钟时浓度达到13 pg/微克，糖尿病大鼠在5小时时达到26 pg/微克。局部应用胰岛素导致血清葡萄糖降低，同时血清猪胰岛素升高。然而，胰岛素的全身吸收似乎并没有促进同侧视网膜中胰岛素的蓄积，原因有二：静脉注射高浓度胰岛素对视网膜胰岛素水平没有明显影响，对断头大鼠应用胰岛素滴眼液仍然导致胰岛素在视网膜中蓄积。
结论
这些结果得出结论，局部应用的胰岛素在正常和糖尿病大鼠的视网膜和视神经中积累，在糖尿病动物中水平保持升高的时间更长。眼部引流引起的全身吸收的胰岛素似乎并未促成这种效应。
PURPOSE
To explore the pharmacokinetics of topical insulin administration in relation to retinal and optic nerve retention.
METHODS
Insulin eye drops (approximately 15 microL: 0.75% porcine insulin + 0.5% permeation enhancer) were applied to the eyes of normal and diabetic rats. The rats were killed at various intervals up to 16 hours, and the retinas and optic nerves from both eyes were analyzed for the presence of insulin in an ELISA. The extent to which systemically absorbed insulin accounted for the findings of insulin in the retina was explored by examining the effects of intravenously injected insulin on retinal insulin levels and by examining the effects of eye drop administration in decapitated rats.
RESULTS
Insulin levels rose significantly and peaked in the retina of normal rats 20 minutes after eye drop application (0.7 pg/microg; P < 0.00001). Levels in diabetic retinas peaked at 60 minutes (0.66 pg/microg; P < 0.004) and remained elevated for a longer period than in normal rats. The contralateral retina showed delayed accumulation of lesser amounts of insulin in both normal and diabetic rats. Significant elevations also occurred in the optic nerves in normal and diabetic rats, with concentrations reaching 13 pg/microg in normal rats at 20 minutes and 26 pg/microg in diabetic rats at 5 hours. Topical insulin application resulted in a decrease in serum glucose concomitant with an increase in serum porcine insulin. It did not appear, however, that the systemic absorption of insulin contributed to the accumulation of insulin in the ipsilateral retinas, for two reasons: The intravenous injection of a high concentration of insulin did not appreciably influence retinal insulin levels, and the application of insulin eye drops to decapitated rats still resulted in the accumulation of insulin in the retina.
CONCLUSIONS
These results led to the conclusion that topically applied insulin accumulates in the retina and optic nerve in normal and diabetic rats, with levels remaining elevated longer in diabetic animals. It did not appear that systemically absorbed insulin, resulting from ocular drainage, contributed to this effect.
影响因子：
--
作者：
MUGGE, A;ELWELL, JH;HARRISON, DG
通讯作者：
HARRISON, DG
通过眼部途径慢性全身输送胰岛素。
DOI：
10.1089/jop.1993.9.85
发表时间：
1993
期刊：
Journal of ocular pharmacology
影响因子：
--
作者：
Chiou,GC;Li,BH
通讯作者：
Li,BH
jun 蛋白在胚胎鸡视网膜中胰岛素刺激胆碱乙酰转移酶中的因果作用。
DOI：
10.1006/bbrc.1997.6374
发表时间：
1997
期刊：
Biochemical and biophysical research communications.
影响因子：
--
作者：
Ren,Y;Holdengreber,V;Ben-Shaul,Y;Shah,BH;Varanasi,J;Hausman,RE
通讯作者：
Hausman,RE