Introduction: The ghrelin gene products ghrelin and obestatin (Ob) protect mice from STZ-induced β-cell death, inflammation and STZ-induced diabetes. A possible event is ghrelin/Ob-induced regeneration of damaged β-cell population through the recruitment of pancreatic progenitor cells (PPC). We hypothesized that Ob affects proliferation and endocrine commitment of PPC within the islets of Langerhans.
Methods: Islets of Langerhans were isolated from pancreas of 6 months old mice and plated for enrichment. Enriched islets were cultured to permit adhesion and stimulate islet-derived cell proliferation (emersion phase). Part of these islets were chronically treated with 100 nM Ob. After a week, culture medium was changed into a serum-free medium supplemented with leukaemia inhibitory factor and fibroblast growth factor 2 to allow proliferation of undifferentiated cells. The expression of staminal and endocrine markers was studied for the next 15 days. During this period cells proliferated (proliferation phase) and aggregated into islet-like cell clusters (ILCC) (differentiation phase).
Results: During the emersion phase Ob treatment increased proliferation of β-cells, but not that of α-cells and of cells expressing Nestin, Ngn3, PDX1, Oct4. At the end of the proliferation phase, Ob-treated cells expressing Nestin or Oct4 highly proliferated, while cells clustering into ILCC expressed more Ngn3 with respect to control. At the end of the differentiation phase Ob-ILCC expressed higher levels of insulin and glucagon. Furthermore, glucose-induced insulin release was increased. Ob effect depended on its modulation of specific signalling molecules essential to endocrine pancreas development.
Conclusions: Ob efficiently stimulated islet-derived cell proliferation and precursor cell differentiation into novel insulin and glucagon secreting ILCC. Thus, in vivo, Ob might ameliorate diabetic conditions through stimulation of PPC. Ob may also improve in vitro islet generation for transplantation purpose.
Note: The correct list of authors is as given above and not as appears in the printed version of the abstract book
30 Apr - 04 May 2011
European Society of Endocrinology