Betatrophin: a hormone that controls pancreatic β cell proliferation

Cell. 2013 May 9;153(4):747-58. doi: 10.1016/j.cell.2013.04.008. Epub 2013 Apr 25.


Replenishing insulin-producing pancreatic β cell mass will benefit both type I and type II diabetics. In adults, pancreatic β cells are generated primarily by self-duplication. We report on a mouse model of insulin resistance that induces dramatic pancreatic β cell proliferation and β cell mass expansion. Using this model, we identify a hormone, betatrophin, that is primarily expressed in liver and fat. Expression of betatrophin correlates with β cell proliferation in other mouse models of insulin resistance and during gestation. Transient expression of betatrophin in mouse liver significantly and specifically promotes pancreatic β cell proliferation, expands β cell mass, and improves glucose tolerance. Thus, betatrophin treatment could augment or replace insulin injections by increasing the number of endogenous insulin-producing cells in diabetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adipose Tissue, White / metabolism
  • Amino Acid Sequence
  • Angiopoietin-like Proteins
  • Animals
  • Cell Proliferation*
  • Female
  • Glucose / metabolism
  • Humans
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Pancreas / cytology*
  • Pancreas / metabolism
  • Peptide Hormones / chemistry
  • Peptide Hormones / genetics
  • Peptide Hormones / metabolism*
  • Peptides / administration & dosage
  • Receptor, Insulin / antagonists & inhibitors
  • Sequence Alignment


  • ANGPTL8 protein, human
  • ANGPTL8 protein, mouse
  • Angiopoietin-like Proteins
  • Peptide Hormones
  • Peptides
  • S961 peptide
  • Receptor, Insulin
  • Glucose

Associated data

  • GEO/GSE45694