How does glucagon-like peptide 1 stimulate human β-cell proliferation? A lesson from islet graft experiments

Journal of Diabetes Investigation
Yoshio Fujitani

Abstract

The incidence of type 2 diabetes increases with age. The age-dependent decline in functional β-cell mass contributes to the increased risk of onset of diabetes, reflecting the central role of pancreatic β-cells in glucose homeostasis. Indeed, the replication rate of human and rodent β-cells is known to decline sharply with age, and such a characteristic of β-cells might explain the increased onset of type 2 diabetes in the older population. The molecular mechanism involved in the age-dependent decline of β-cell proliferation has been extensively studied, mainly using rodents and in vitro culture systems, but its molecular basis is still largely unknown. A mechanism by which glucagon-like peptide-1 receptor activation induces human β-cell proliferation only within a restricted time window was recently suggested in a study in which human islets were grafted into immunodeficient mice. The authors found that the mitogenic effects of exendin-4 require calcineurin/nuclear factor of activated T-cells signaling, and that only in juvenile islets, exendin-4 induced the expression of nuclear factor of activated T-cells signaling components, as well as downstream target genes that facilitate β-cell proliferation. These findings provide a m...Continue Reading

References

Jul 21, 2012·Developmental Cell·William R GoodyerSeung K Kim
May 21, 2013·Cell Metabolism·Jonathan E Campbell, Daniel J Drucker
Sep 18, 2017·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Gauri Dhir, Kenneth Cusi
Sep 19, 2017·The Journal of Clinical Investigation·Chunhua DaiAlvin C Powers

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Citations

Jul 14, 2019·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·H P T Ammon
Nov 27, 2019·Molecular Metabolism·T D MüllerM H Tschöp

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Methods Mentioned

BETA
electron microscopy
ribonucleic acid sequencing

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