title: ANGPTL8/betatrophin does not control pancreatic beta cell expansion.
abstract: 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.
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA. Electronic address: viktoria.gusarova@regeneron.com.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gusarova
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Alexa
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Erqian
authors.initials: E
authors.lastname: Na
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Panayiotis E
authors.initials: PE
authors.lastname: Stevis
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Bonner-Weir
authors.affiliation: Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Cohen
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Helen H
authors.initials: HH
authors.lastname: Hobbs
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Jesper
authors.initials: J
authors.lastname: Gromada
mesh_terms: D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000378:metabolism
chemical_list: C000595899:ANGPTL8 protein, mouse; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D014280:Triglycerides