1. Human Biology and Medicine
  2. Stem Cells and Regenerative Medicine
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Insulin: Folding mutations suppress early beta-cell proliferation

  1. Honey Modi  Is a corresponding author
  2. James D Johnson  Is a corresponding author
  1. University of British Columbia, Canada
Cite this article as: eLife 2018;7:e43475 doi: 10.7554/eLife.43475
1 figure


Mutations in insulin and endoplasmic reticulum stress reduce the proliferation and the maturation of beta-cells after birth.

(A) The post-natal period (pink) is a unique time window when beta-cells proliferate robustly (blue line) and insulin production (green line) increases (Gregg et al., 2012; Henquin and Nenquin, 2016). After that short pre-weaning period, the proliferation rate drops and the production of insulin stabilizes. (B) When mutations cause insulin to misfold, the genes in an ER stress pathway known as the unfolded protein response are upregulated (green arrow). These mutations also lead to key beta-cell transcription factors being down-regulated, which impairs the maturation of the beta-cells. Meanwhile, the down-regulation of the mTORC1 pathway also leads to a reduction in the number of functional beta-cells (red arrows). Beta-cell stressors can increase the levels of misfolded insulin (orange arrow), while interventions could therapeutically reduce the levels of misfolded insulin (purple inhibitory arrow).

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