The unfolded protein response is required to maintain the integrity of the endoplasmic reticulum, prevent oxidative stress and preserve differentiation in β-cells
2010

The Role of the Unfolded Protein Response in Diabetes

publication Evidence: high

Author Information

Author(s): R J Kaufman, Back S H, Song B, Han J, Hassler J

Primary Institution: Howard Hughes Medical Institute, University of Michigan Medical Center

Hypothesis

The unfolded protein response (UPR) is crucial for maintaining β-cell function and preventing diabetes.

Conclusion

The study suggests that both excessive and insufficient eIF2α phosphorylation lead to oxidative stress, contributing to β-cell failure and diabetes.

Supporting Evidence

  • CHOP nuclear localization was found in pancreata of human obese diabetic individuals.
  • UPR-induced proteins were significantly elevated in islets from patients with type 2 diabetes.
  • Chop deletion improved β-cell survival and function in multiple diabetes models.

Takeaway

When cells in the pancreas can't fold proteins properly, it can lead to diabetes. This study shows how a special response in cells helps manage this problem.

Digital Object Identifier (DOI)

10.1111/j.1463-1326.2010.01281.x

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