First Author | Cai Y | Year | 2014 |
Journal | Diabetologia | Volume | 57 |
Issue | 7 | Pages | 1420-7 |
PubMed ID | 24759958 | Mgi Jnum | J:213745 |
Mgi Id | MGI:5585696 | Doi | 10.1007/s00125-014-3242-8 |
Citation | Cai Y, et al. (2014) IL-6-dependent proliferation of alpha cells in mice with partial pancreatic-duct ligation. Diabetologia 57(7):1420-7 |
abstractText | AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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. |