GSBS Student Publications


High ER stress in beta-cells stimulates intracellular degradation of misfolded insulin

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date


UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Program in Molecular Medicine

Document Type



Life Sciences | Medicine and Health Sciences


Endoplasmic reticulum (ER) stress, which is caused by the accumulation of misfolded proteins in the ER, elicits an adaptive response, the unfolded protein response (UPR). One component of the UPR, the endoplasmic reticulum-associated protein degradation (ERAD) system, has an important function in the survival of ER stressed cells. Here, we show that HRD1, a component of the ERAD system, is upregulated in pancreatic islets of the Akita diabetes mouse model and enhances intracellular degradation of misfolded insulin. High ER stress in beta-cells stimulated mutant insulin degradation through HRD1 to protect beta-cells from ER stress and ensuing death. If HRD1 serves the same function in humans, it may serve as a target for therapeutic intervention in diabetes.

DOI of Published Version



Biochem Biophys Res Commun. 2004 Nov 5;324(1):166-70. Link to article on publisher's site

Journal/Book/Conference Title

Biochemical and biophysical research communications

Related Resources

Link to article in PubMed

PubMed ID