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

C. C. Richardson, K. To, V. L. Foot, A. C. Hauge-Evans, D. Carmignac, M. R. Christie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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-β 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.

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalHormone and Metabolic Research
Volume47
Issue number1
Early online date28 Oct 2014
DOIs
Publication statusPublished - 2015

Keywords

  • delta cells
  • insulin secretion
  • pancreas development
  • pancreatic islets

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