Novel factors modulating human β-cell proliferation.
β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes.
Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, Massachusetts.|Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
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Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, Massachusetts. rohit.kulkarni@joslin.harvard.edu.|Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. rohit.kulkarni@joslin.harvard.edu.|Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts. rohit.kulkarni@joslin.harvard.edu.
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D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D000069448:Denosumab / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors; D006247:Harmine / Q000494:pharmacology; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D053244:Osteoprotegerin / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D015843:Serpins / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D000097603:Dyrk Kinases
D048868:Adaptor Proteins, Signal Transducing; D000069448:Denosumab; D000071679:Glycogen Synthase Kinase 3 beta; D006247:Harmine; D051550:I-kappa B Kinase; D008996:Monoamine Oxidase Inhibitors; D053244:Osteoprotegerin; D010671:Phenylurea Compounds; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D016601:RNA-Binding Proteins; D053246:Receptor Activator of Nuclear Factor-kappa B; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D014363:Tryptamines; D000097603:Dyrk Kinases; C577005:(1H-indol-5-yl)propan-2-amine; C101633:PA2G4 protein, human; C000604999:WS6 compound; C075177:SERPINB1 protein, human
GNF4877; SerpinB1; WS6; harmine; human β-cell proliferation; osteoprotegrin