PUBLICATION

SerpinB1 Promotes Pancreatic ? Cell Proliferation

Authors
El Ouaamari, A., Dirice, E., Gedeon, N., Hu, J., Zhou, J.Y., Shirakawa, J., Hou, L., Goodman, J., Karampelias, C., Qiang, G., Boucher, J., Martinez, R., Gritsenko, M.A., De Jesus, D.F., Kahraman, S., Bhatt, S., Smith, R.D., Beer, H.D., Jungtrakoon, P., Gong, Y., Goldfine, A.B., Liew, C.W., Doria, A., Andersson, O., Qian, W.J., Remold-O'Donnell, E., Kulkarni, R.N.
ID
ZDB-PUB-151225-2
Date
2016
Source
Cell Metabolism   23(1): 194-205 (Journal)
Registered Authors
Karampelias, Christos
Keywords
none
MeSH Terms
  • Cell Proliferation*
  • Humans
  • Serpins/physiology*
  • Liver/metabolism
  • Animals
  • Signal Transduction
  • Receptor, Insulin/genetics
  • Receptor, Insulin/metabolism
  • Zebrafish
  • Insulin Resistance
  • Cells, Cultured
  • Insulin-Secreting Cells/physiology*
  • Male
  • Mice, Knockout
  • Mice, Inbred C57BL
(all 15)
PubMed
26701651 Full text @ Cell Metab.
Abstract
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.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
s892Tg; s949Tgchemical treatment: metronidazoleDay 4
1 - 1 of 1
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s892TgTransgenic Insertion
    s949TgTransgenic Insertion
      s950TgTransgenic Insertion
        s960TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          No data available
          Fish
          Fish
          s892Tg; s949Tg
          1 - 1 of 1
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          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          CFPEFGCFP
          DsRedEFGDsRed
          GFPEFGGFP
          KaedeEFGKaede
          mCherryEFGmCherry
          NTREFGNTR
          1 - 6 of 6
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          Mapping
          No data available
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          Citation
          El Ouaamari, A., Dirice, E., Gedeon, N., Hu, J., Zhou, J.Y., Shirakawa, J., Hou, L., Goodman, J., Karampelias, C., Qiang, G., Boucher, J., Martinez, R., Gritsenko, M.A., De Jesus, D.F., Kahraman, S., Bhatt, S., Smith, R.D., Beer, H.D., Jungtrakoon, P., Gong, Y., Goldfine, A.B., Liew, C.W., Doria, A., Andersson, O., Qian, W.J., Remold-O'Donnell, E., Kulkarni, R.N. (2016) SerpinB1 Promotes Pancreatic ? Cell Proliferation. Cell Metabolism. 23(1):194-205.