title: In vitro proliferation of adult human beta-cells.
abstract: A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells") population were plated on extracellular matrix from rat (804G) and human bladder carcinoma cells (HTB9) or bovine corneal endothelial ECM (BCEC). Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted) or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted), independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05).These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. sabine.rutti@unige.ch
authors.forename: Sabine
authors.initials: S
authors.lastname: Rutti
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Sauter
authors.forename: Karim
authors.initials: K
authors.lastname: Bouzakri
authors.forename: Richard
authors.initials: R
authors.lastname: Prazak
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Halban
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D051381:Rats; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D052216:Glucagon-Like Peptide 1