, Volume 57, Issue 7, pp 1420–1427 | Cite as

IL-6-dependent proliferation of alpha cells in mice with partial pancreatic-duct ligation

  • Ying Cai
  • Yixing Yuchi
  • Sofie De Groef
  • Violette Coppens
  • Gunter Leuckx
  • Luc Baeyens
  • Mark Van de Casteele
  • Harry HeimbergEmail author



IL-6 was recently shown to control alpha cell expansion. As beta cells expand following partial pancreatic-duct ligation (PDL) in adult mice, we investigated whether PDL also causes alpha cells to expand and whether IL-6 signalling is involved. As alpha cells can reprogramme to beta cells in a number of beta cell (re)generation models, we examined whether this phenomenon also exists in PDL pancreas.


Total alpha cell volume, alpha cell size and total glucagon content were evaluated in equivalent portions of PDL- and sham-operated mouse pancreases. Proliferation of glucagon+ cells was assessed by expression of the proliferation marker Ki67. Inter-conversions between alpha and beta cells were monitored in transgenic mice with conditional cell-type-specific labelling. The role of IL-6 in regulating alpha cell proliferation was evaluated by in situ delivery of an IL-6-inactivating antibody.


In response to PDL surgery, alpha cell volume in the ligated tissue was increased threefold, glucagon content fivefold and alpha cell size by 10%. Activation of alpha cell proliferation in PDL pancreas required IL-6 signalling. A minor fraction of alpha cells derived from beta cells, whereas no evidence for alpha to beta cell conversion was obtained.


In PDL-injured adult mouse pancreas, new alpha cells are generated mainly by IL-6-dependent self-duplication and seldom by reprogramming of beta cells.


Alpha cell Beta cell Diabetes Glucagon IL-6 Islet Neogenesis Partial duct ligation Proliferation Reprogramming 





Glucagon-like peptide-1


Green fluorescent protein




V-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (avian)


Partial pancreatic-duct ligation

Pro-hormone convertases 1/3 and 2

PC1/3 and PC2


Reverse tetracycline transactivator


Signal transducer and activator of transcription 3




Yellow fluorescent protein



We thank A. Demarré, V. Laurysens, J. de Jonge, E. Quartier, R. de Proft and G. Schoonjans (Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium) for technical assistance, and P. Herrera (University of Geneva, Geneva, Suisse) for sharing the Gcg rtTA /TetO Cre mice.


Financial support was from the VUB Research Council (HH, MVdC), the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) (HH, VC), the Chinese Scholarship Council (YY), the Innovative Medicines Initiative Joint Undertaking under grant agreement number 155005 (IMIDIA) composed of financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution (HH), Stichting Diabetes Onderzoek Nederland (HH), the Fund for Scientific Research Flanders (FWO) (HH, SDG) and the Interuniversity Attraction Pole networks (HH).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

All authors were involved in the acquisition, analysis or interpretation of data and drafting of the manuscript. YC, YY, MVdC and HH were involved in the study concept and design and critical revision of the manuscript. All authors approved the final version of the manuscript.

HH is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Supplementary material

125_2014_3242_MOESM1_ESM.pdf (406 kb)
ESM Fig. 1 (PDF 405 kb)
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ESM Fig. 2 (PDF 392 kb)
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ESM Fig. 3 (PDF 232 kb)
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ESM Fig. 4 (PDF 625 kb)
125_2014_3242_MOESM5_ESM.pdf (241 kb)
ESM Fig. 5 (PDF 241 kb)
125_2014_3242_MOESM6_ESM.pdf (47 kb)
ESM Table 1 (PDF 47 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ying Cai
    • 1
  • Yixing Yuchi
    • 1
  • Sofie De Groef
    • 1
  • Violette Coppens
    • 1
  • Gunter Leuckx
    • 1
  • Luc Baeyens
    • 1
  • Mark Van de Casteele
    • 1
  • Harry Heimberg
    • 1
    Email author
  1. 1.Diabetes Research CenterVrije Universiteit BrusselBrusselsBelgium

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