ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2022) 19 10.8 | DOI: 10.1530/ey.19.10.8


Nat Med. 2021 Dec;27(12):2104-2107. https://pubmed.ncbi.nlm.nih.gov/34887578/

Brief Summary: This study used single-cell transcriptomic analyses to generate a cell atlas of the human fetal and neonatal small intestine. Notably, the authors identified a subset of fetal enteroendocrine K/L cells (named FIKL) that express high levels of insulin and other beta cell genes.

This study explored whether insulin is expressed in the enteroendocrine cells of the human fetus. There is a strong rationale for focusing on the fetal gut due to the shared developmental origins between the pancreas and small intestine as well as common transcriptional programmes and stimulus-secretion mechanisms between the intestinal enteroendocrine and pancreatic islet cells (1). Comparative analysis between fetal and neonatal cells led to the remarkable finding that, in the fetal small intestine enteroendocrine K/L cells expressed high levels of the insulin gene, along with other typical beta cell genes. Although the newborn’s small intestines also contained K/L cells, these did not express insulin.

While all cells contain the insulin gene, only pancreatic beta cells can secrete insulin. Hence, this finding of additional insulin-expressing fetal cells is notable. At present, the mechanisms that turn off FIKL cell’s insulin-making program at birth remain unknown, as well as whether this can be turned back on. The potential paracrine or systemic role of the FIKL cells also remains to be clarified. The finding that the FIKL cells were not detected in all analysed samples raises the question as to whether their expression might be driven by specific environmental conditions, such maternal gestational diabetes and exposure to high glucose levels during fetal life.

Overall, these findings create new hopes for the identification of extra-pancreatic sources of beta cells, which is a promising avenue for the treatment of diabetes.

Reference: 1. Jennings RE, Berry AA, Strutt JP, Gerrard DT, Hanley NA. Human pancreas development. Development 2015;142:3126–3137.

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