New sources of pancreatic beta-cells.
Two major initiatives are under way to correct the beta-cell deficit of diabetes: one would generate beta-cells ex vivo that are suitable for transplantation, and the second would stimulate regeneration of beta-cells in the pancreas. Studies of ex vivo expansion suggest that beta-cells have a potential for dedifferentiation, expansion, and redifferentiation. Work with mouse and human embryonic stem (ES) cells has not yet produced cells with the phenotype of true beta-cells, but there has been recent progress in directing ES cells to endoderm. Putative islet stem/progenitor cells have been identified in mouse pancreas, and formation of new beta-cells from duct, acinar and liver cells is an active area of investigation. Peptides, including glucagon-like peptide-1/exendin-4 and the combination of epidermal growth factor and gastrin, can stimulate regeneration of beta-cells in vivo. Recent progress in the search for new sources of beta-cells has opened promising new opportunities and spawned clinical trials.
Bonner-Weir
Susan
S
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA. susan.bonner-weir@joslin.harvard.edu
Weir
Gordon C
GC
D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000473:pathology / Q000628:therapy*; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D000077270:Exenatide; D005755:Gastrins / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D010179:Pancreas / Q000166:cytology / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D012038:Regeneration; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D014688:Venoms / Q000494:pharmacology
D005755:Gastrins; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D014688:Venoms; D004815:Epidermal Growth Factor; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide