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TGFβ receptor signaling is essential for inflammation-induced but not β-cell workload-induced β-cell proliferation.
- Source :
-
Diabetes [Diabetes] 2013 Apr; Vol. 62 (4), pp. 1217-26. Date of Electronic Publication: 2012 Dec 17. - Publication Year :
- 2013
-
Abstract
- Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult β-cell homeostasis is not well defined. Here, we ablated TGFβ receptor I and II genes in mice undergoing two surgical β-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for β-cell proliferation, increased β-cell workload and local inflammation, respectively. Our data suggest that TGFβ receptor signaling is necessary for baseline β-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased β-cell workload are both stimulants for β-cell proliferation but are TGFβ receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGFβ receptor-deleted mouse model, we have identified two distinct pathways that regulate adult β-cell proliferation. Our study thus provides important information for understanding β-cell proliferation during normal growth and in pancreatic diseases.
- Subjects :
- Animals
Cell Proliferation
Glucose pharmacology
Insulin pharmacology
Insulin-Secreting Cells cytology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pancreatectomy methods
RNA-Directed DNA Polymerase
Receptors, Transforming Growth Factor beta genetics
Signal Transduction
Transforming Growth Factor beta genetics
Insulin-Secreting Cells metabolism
Receptors, Transforming Growth Factor beta metabolism
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 62
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 23248173
- Full Text :
- https://doi.org/10.2337/db12-1428