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• W2071776215 abstract "Pancreatic islet transplantation as a treatment for type 1 diabetes is limited by human donor tissue availability. We investigated whether the β-cell mass in human isolated islets could be expanded by treatments with glucagon-like peptide-1 (GLP-1) and gastrin, peptides reported to stimulate β-cell growth in mice and rats with deficits in β-cell mass. Human islets with low endocrine cell purity (7% β-cells, 4% α-cells) and abundant exocrine cells (29% duct cells and 25% acinar cells) were implanted under the renal capsule of nonobese diabetic-severe combined immune deficiency (NOD-scid) mice made diabetic with streptozotocin. The mice were treated with GLP-1 and gastrin, separately and together, daily for 5 weeks. Blood glucose was significantly reduced only in mice implanted with human pancreatic cells and treated with GLP-1 plus gastrin. Correction of hyperglycemia was accompanied by increased insulin content in the human pancreatic cell grafts as well as by increased plasma levels of human C-peptide in the mice. Immunocytochemical examination revealed a fourfold increase in insulin-positive cells in the human pancreatic cell grafts in GLP-1 plus gastrin-treated mice, and most of this increase was accounted for by the appearance of cytokeratin 19-positive pancreatic duct cells expressing insulin. We conclude that combination therapy with GLP-1 and gastrin expands the β-cell mass in human islets implanted in immunodeficient diabetic mice, largely from pancreatic duct cells associated with the islets, and this is sufficient to ameliorate hyperglycemia in the mice." @default.
• W2071776215 created "2016-06-24" @default.
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• W2071776215 date "2008-06-01" @default.
• W2071776215 modified "2023-10-16" @default.
• W2071776215 title "Combination Therapy with Glucagon-Like Peptide-1 and Gastrin Induces β-Cell Neogenesis from Pancreatic Duct Cells in Human Islets Transplanted in Immunodeficient Diabetic Mice" @default.
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• W2071776215 doi "https://doi.org/10.3727/096368908786092775" @default.
• W2071776215 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18819251" @default.
• W2071776215 hasPublicationYear "2008" @default.
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