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Published on: July 16, 2016
Proinsulin in development: New roles for an ancient prohormone
C Hernández-Sánchez1, A Mansilla, E J de la Rosa
1Group of Growth Factors in Vertebrate Development, Centre of Biological Investigations (CIB), Spanish Council for Research (CSIC), Ramiro de Maeztu 9, E-28040 Madrid, Spain. chernandez@cib.csic.es
Diabetologia
|April 6, 2006
Summary
Insulin, beyond glucose control, acts as a crucial developmental factor in embryos, promoting survival and morphogenesis. Its embryonic roles are mediated by proinsulin, with regulated expression preventing developmental harm.
Area of Science:
- Developmental Biology
- Endocrinology
- Molecular Biology
Background:
- Insulin is traditionally recognized as a key anabolic hormone for glucose homeostasis in postnatal life.
- Pancreatic beta cells are considered the primary site of insulin biosynthesis, a model for tissue-specific gene expression.
- However, proinsulin has been detected in embryonic stages and extrapancreatic tissues, suggesting broader roles.
Purpose of the Study:
- To investigate the non-metabolic functions of insulin and proinsulin during embryonic development.
- To understand the role of insulin-like peptides in early development and morphogenesis.
- To elucidate the regulatory mechanisms of insulin/proinsulin levels during embryogenesis.
Main Methods:
- Analysis of proinsulin mRNA and protein expression in embryonic tissues.
- Phylogenetic studies on insulin-like peptides in development.
- Investigation of proinsulin's effects on cell proliferation, survival, and cardiogenesis in early embryos.
- Examination of alternative embryonic proinsulin transcripts and their translational activity.
Main Results:
- Proinsulin and insulin-like peptides are present and functional before pancreas formation, contributing to normal development.
- During embryogenesis, insulin acts as a survival factor and is involved in early morphogenesis.
- Proinsulin, independent of metabolic activity, promotes neuroretina proliferation, cell survival, and cardiogenesis.
- Embryonic insulin/proinsulin levels are tightly regulated; excess is detrimental to morphogenesis.
Conclusions:
- Insulin/proinsulin plays critical, non-metabolic roles in embryonic development, including survival and morphogenesis.
- The regulation of embryonic proinsulin expression, including alternative transcripts, is vital for preventing developmental abnormalities.
- These findings expand the understanding of insulin's functions beyond metabolic control, highlighting its significance in early vertebrate development.
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