ANGPTL8/Betatrophin Does Not Control Pancreatic Beta Cell Expansion

被引：240

作者：

Gusarova, Viktoria ^{[1
]}

Alexa, Corey A. ^{[1
]}

Na, Erqian ^{[1
]}

Stevis, Panayiotis E. ^{[1
]}

Xin, Yurong ^{[1
]}

Bonner-Weir, Susan ^{[2
]}

Cohen, Jonathan C. ^{[3
]}

Hobbs, Helen H. ^{[4
,5
]}

Murphy, Andrew J. ^{[1
]}

Yancopoulos, George D. ^{[1
]}

Gromada, Jesper ^{[1
]}

机构：

[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

[2] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA

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

[4] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[5] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA

来源：

CELL | 2014年 / 159卷 / 03期

关键词：

GLUCOSE-INFUSION; INSULIN-RESISTANCE; BETATROPHIN; MICE; REGENERATION; INDIVIDUALS; REPLICATION; HYPERPLASIA; METABOLISM; DISEASE;

D O I：

10.1016/j.cell.2014.09.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Recently, it was reported that angiopoietin-like protein 8 (ANGPTL8) was the long-sought "betatrophin" that could control pancreatic beta cell proliferation. However, studies of Angptl8(-/-) mice revealed profound reduction of triglyceride levels, but no abnormalities in glucose homeostasis. We now report that Angptl8(-/-) mice undergo entirely normal beta cell expansion in response to insulin resistance resulting from either a high-fat diet or from the administration of the insulin receptor antagonist S961. Furthermore, overexpression of ANGPTL8 in livers of mice doubles plasma triglyceride levels, but does not alter beta cell expansion nor glucose metabolism. These data indicate that ANGPTL8 does not play a role in controlling beta cell growth, nor can it be given to induce such expansion. The findings that plasma triglyceride levels are reduced by Angptl8 deletion and increased following ANGPTL8 overexpression support the possibility that inhibition of ANGPTL8 represents a therapeutic strategy for hypertriglyceridemia.

引用

页码：691 / 696

页数：6

共 22 条

[1]

Glucose infusion in mice -: A new model to induce β-cell replication [J].