Abstract
The authors used mouse conditional gene knock-out models to investigate the role of Insulin-like growth factor-2 (Igf2) in pancreatic growth and function. When Igf2 was deleted specifically in mesenchyme-derived cells (but not when deleted in exocrine and endocrine cells), the entire pancreas was smaller and showed reduced exocrine and endocrine functions. These mice showed postnatal whole-body growth restriction and the female mice developed glucose intolerance when they became pregnant. Conversely, increased IGF2 levels in the mesenchyme-derived cells increased pancreatic size.
Highlights
The mammalian pancreas plays a central role in energy homeostasis, which is achieved by functionally and morphologically distinct exocrine and endocrine components
The pancreas is formed of two main components: the exocrine pancreas and the endocrine pancreas
In this study, using mouse genetic engeneering, we explored the roles played by a hormone-like gene called insulin-like growth factor 2 (Igf2), that is similar in structure to insulin, and is active only on the chromosome inherited from the father
Summary
The mammalian pancreas plays a central role in energy homeostasis, which is achieved by functionally and morphologically distinct exocrine and endocrine components. The size of the pancreas is thought to be fixed early in development, limited by the size of the progenitor cell pool that is established in the developing pancreatic bud [1]. Mesenchymal cells overlie the developing pancreatic bud and provide critical signals for the expansion of both precursors and differentiated endocrine and exocrine cells [2]. These cells are present throughout pancreas organogenesis, but the relative proportion of mesenchyme to epithelium changes, with a dramatic reduction over time, as the mesenchyme differentiates into more specialized cell types such as pericytes [3] and epithelial cells expand. The factors required for cell fate decisions that specify individual pancreas cell type subsets are fairly well established but less is known about signalling pathways involved in proliferation and survival of cell types
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