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.
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
Susan
S
Bonner-Weir
Gordon C
GC
Weir
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