In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats

被引：39

作者：

Chen, Jiaxi ^{[1
]}

Chen, Shuyuan ^{[2
]}

Huang, Pintong ^{[3
]}

Meng, Xing-Li ^{[2
]}

Clayton, Sandra ^{[4
]}

Shen, Jin-Song ^{[2
]}

Grayburn, Paul A. ^{[2
,5
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Sch Med, Dallas, TX 75390 USA

[2] Baylor Univ, Med Ctr, Baylor Res Inst, Dallas, TX USA

[3] Zhejiang Univ, Coll Med, Dept Ultrasonog, Affiliated Hosp 2, Hangzhou 310003, Zhejiang, Peoples R China

[4] Baylor Inst Immunol Res, Imaging Core Facil, Dallas, TX USA

[5] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Div Cardiol,Dept Internal Med, Dallas, TX 75226 USA

来源：

DIABETOLOGIA | 2015年 / 58卷 / 05期

关键词：

ANGPTL8; Beta cell islets; Betatrophin; Diabetes; Gene delivery; Proliferation; ADULT PANCREATIC PROGENITORS; MEDIATES ISLET REGENERATION; ANGIOPOIETIN-LIKE PROTEIN; TRANSGENE EXPRESSION; BETATROPHIN; DIFFERENTIATION; PROLIFERATION; THERAPY; LIPASIN; ANGPTL8/BETATROPHIN;

D O I：

10.1007/s00125-015-3521-z

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Aims/hypothesis ANGPTL8 is a circulatory hormone secreted from liver and adipose tissue that promotes pancreatic beta cell proliferation and interferes with triacylglycerol metabolism in mice. The clinical significance of its effects on inducing beta cell proliferation is limited because it causes severe hypertriacylglycerolaemia. Methods We employed ultrasound-targeted microbubble destruction (UTMD) to deliver human ANGPTL8 gene plasmids to the pancreas, liver and skeletal muscle of normal adult rats. Results Human ANGPTL8 was consistently detected in the circulation 1 month after UTMD. ANGPTL8 gene delivery promoted the proliferation of adult and aged beta cells, expanded the beta cell mass, improved glucose tolerance and increased the fasting blood insulin level after UTMD treatment without causing severe hypertriacylglycerolaemia. ANGPTL8 gene therapy significantly alleviated but did not totally reverse STZ-induced diabetes in a rat model. Conclusions/interpretation ANGPTL8 induced adult and aged beta cell regeneration in a rat model.

引用

页码：1036 / 1044

页数：9

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