Pancreatic β-Cells express the fetal islet hormone gastrin in rodent and human diabetes

Tehila Dahan, Oren Ziv, Elad Horwitz, Hai Zemmour, Judith Lavi, Avital Swisa, Gil Leibowitz, Frances M. Ashcroft, Peter In t. Veld, Benjamin Glaser, Yuval Dor

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

β-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of β-Cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin+ cells, gastrin expression in humans with T2D occurs in both insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated β-Cells after exposure to severe hyperglycemia. Gastrin expression in adult β-Cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of β-Cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human β-Cell reprogramming in diabetes.

Original languageEnglish
Pages (from-to)426-436
Number of pages11
JournalDiabetes
Volume66
Issue number2
DOIs
StatePublished - 1 Feb 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 by the American Diabetes Association.

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