title: Weaning triggers a maturation step of pancreatic β cells.
abstract: Because tissue regeneration deteriorates with age, it is generally assumed that the younger the animal, the better it compensates for tissue damage. We have examined the effect of young age on compensatory proliferation of pancreatic β cells in vivo. Surprisingly, β cells in suckling mice fail to enter the cell division cycle in response to a diabetogenic injury or increased glycolysis. The potential of β cells for compensatory proliferation is acquired following premature weaning to normal chow, but not to a diet mimicking maternal milk. In addition, weaning coincides with enhanced glucose-stimulated oxidative phosphorylation and insulin secretion from islets. Transcriptome analysis reveals that weaning increases the expression of genes involved in replication licensing, suggesting a mechanism for increased responsiveness to the mitogenic activity of high glucose. We propose that weaning triggers a discrete maturation step of β cells, elevating both the mitogenic and secretory response to glucose.
authors: Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Miri
authors: M
authors: Stolovich-Rain
authors: Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Jonatan
authors: J
authors: Enk
authors: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Jonas
authors: J
authors: Vikesa
authors: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Finn Cilius
authors: FC
authors: Nielsen
authors: Monique and Jacques Roboh Department of Genetic Research and the Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Ann
authors: A
authors: Saada
authors: Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors: Benjamin
authors: B
authors: Glaser
authors: Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. Electronic address: yuvald@ekmd.huji.ac.il.
authors: Yuval
authors: Y
authors: Dor
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014886:Weaning
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose