Long-term insulinotropic activity of glucagon-like peptide-1/polymer conjugate on islet microcapsules

被引:8
作者
Kim, S
Bae, YH
机构
[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84108 USA
[2] Gwangju Inst Sci & Technol, Dept Mat Sci & Engn, Ctr Biomat & Biotechnol, Kwangju, South Korea
来源
TISSUE ENGINEERING | 2004年 / 10卷 / 11-12期
关键词
D O I
10.1089/ten.2004.10.1607
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The biohybrid artificial pancreas (BAP), a promising therapy for type 1 diabetes, faces several obstacles such as the need for a large implantation volume of encapsulated islets because of low functionality. To address such problems, in this study we examined long-term insulinotropic activity of glucagon-like peptide-1 (GLP-1)/polymer conjugate [VAPG: poly(N-vinylpyrrolidone-co-acrylic acid-g-PEG) (VAP) -GLP-1] as well as GLP-1/Zn2+ crystal by coencapsulation with islets. Microcapsules with VAPG or crystal produced round-shaped beads whereas free GLP-1 showed poor capsule morphology. A perfusion experiment suggested that VAPG showed higher bioactivity than did microcapsules with GLP-1/Zn2+. In long-term culture (200 mg of glucose/dL [G]), VAPG also enhanced insulinotropic activity over 5 weeks compared with the crystal form of GLP-1. However, maintenance of the high bioactivity of VAPG suddenly declined after week 5, possibly because of degradation, metabolism, and overstimulation. Basal (50 G) and glucose-stimulated (300 G) levels of insulin secretion confirmed a see-saw pattern in which the VAPG gradually decreased insulin secretion from encapsulated islets and then fell below the insulin level secreted from microcapsules containing GLP-1/Zn2+ crystal. Viability of the microcapsulated islets of each group was not significantly different. Consequently, the coencapsulation of VAPG or GLP-1/Zn2+ crystal can be a potential approach to reducing BAP volume with further optimization of activity duration.
引用
收藏
页码:1607 / 1616
页数:10
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