Increased perinatal remodelling of the pancreas in somatostatin-deficient mice: Potential role of transforming growth factor-beta signalling in regulating beta cell growth in early life

Richardson, C. C. and To, K. and Foot, V. L. and Hauge-Evans, A. C. and Carmignac, D. and Christie, Michael (2015) Increased perinatal remodelling of the pancreas in somatostatin-deficient mice: Potential role of transforming growth factor-beta signalling in regulating beta cell growth in early life. Hormone and Metabolic Research, 47 (1). pp. 56-63. ISSN 0018-5043

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Increased perinatal remodelling of the pancreas in somatostatin-deficient mice: Potential role of transforming growth factor-beta signalling in regulating beta cell growth in early life

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Abstract

Early postnatal life is a critical period for development of the endocrine pancreas, involving remodelling of islet cells and maturation of secretory responses. Factors that regulate these processes are undefined. Somatostatin-secreting delta-cells are abundant in the developing pancreas and, because somatostatin inhibits growth, the hormone may regulate islet expansion in early life. The aim of this study was to investigate effects of somatostatin-deficiency on proliferation, apoptosis and pancreas expansion in the first 3 weeks of life in mice. Pancreases from control or somatostatin-knockout mice were analysed for beta cell, alpha cell and pancreatic volumes by morphometry, proliferation by BrdU incorporation and apoptosis by TUNEL labelling. Signalling pathways associated with proliferation and apoptosis were studied by immunohistochemistry and Western blotting. Knockout mice grew normally in the first 3 weeks of life, but had high circulating insulin that normalised by day 21. Beta cell, alpha cell and pancreatic volumes were decreased in knockout mice, accompanied by reduced proliferation and increased apoptosis in the pancreas. Decreased growth was not due to impaired Akt signalling, as Akt phosphorylation and nuclear cyclin-D2 increased in the knockout pancreas. Levels of TGF-β1, a factor implicated in tissue remodelling, together with SMAD phosphorylation through which TGF-β1 mediates its effects, were increased in the knockout pancreas. Beta cell expansion was impaired in knockout mice, potentially compensating for increased insulin secretion from islets lacking inhibitory effects of somatostatin, and was associated with increased TGF-β1 levels. TGF-β1 may represent an important regulator of beta cell mass in early life. © Georg Thieme Verlag KG Stuttgart New York.

Keywords:broxuridine, cyclin D2, glucose, insulin, protein kinase B, protein p21, protein p27, Smad protein, somatostatin, transforming growth factor beta, transforming growth factor beta1, animal experiment, apoptosis, Article, cell expansion, cell growth, cell proliferation, controlled study, enzyme phosphorylation, female, glucose blood level, glucose tolerance, immunohistochemistry, insulin blood level, insulin release, male, mouse, nick end labeling, nonhuman, organ size, pancreas islet alpha cell, pancreas islet beta cell, perinatal development, priority journal, protein phosphorylation, signal transduction, Western blotting, Mus, JCNotOpen
Subjects:B Subjects allied to Medicine > B120 Physiology
Divisions:College of Science > School of Life Sciences
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ID Code:18109
Deposited On:31 Jul 2015 08:35

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