SerpinB1 Promotes Pancreatic β Cell Proliferation

Cell Metab. 2016 Jan 12;23(1):194-205. doi: 10.1016/j.cmet.2015.12.001. Epub 2015 Dec 15.


Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates β cell proliferation in humans, mice, and zebrafish. Small-molecule compounds, that partially mimic serpinB1 effects of inhibiting elastase activity, enhanced proliferation of β cells, and mice lacking serpinB1 exhibit attenuated β cell compensation in response to insulin resistance. Finally, SerpinB1 treatment of islets modulated proteins in growth/survival pathways. Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional β cell mass in patients with diabetes.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation*
  • Cells, Cultured
  • Humans
  • Insulin Resistance
  • Insulin-Secreting Cells / physiology*
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Serpins / physiology*
  • Signal Transduction
  • Zebrafish


  • Serpinb1a protein, mouse
  • Serpins
  • Receptor, Insulin