Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival.

By H. Harding, Huiqing Zeng, Yuhong Zhang, Rivka Jungries, Peter Chung, Heidi Plesken, D. Sabatini, D. Ron. Molecules and Cells, 2001

1,277 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/4dc1e9b00b4cc8147c564e179da8a15d5f42c4e4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. R. Kaufman
2. G. Hotamışlıgil
3. C. Hetz
4. D. Ron
5. Peter Walter
6. J. Malhotra
7. Afshin Samali
8. A. Gorman

In Molecular Biology

1. R. Kaufman
2. G. Hotamışlıgil
3. D. Ron
4. C. Hetz
5. H. Harding
6. Peter Walter
7. Afshin Samali
8. A. Gorman

In Surgery

1. R. Kaufman
2. G. Hotamışlıgil
3. C. Hetz
4. D. Ron
5. Peter Walter
6. S. S. Cao
7. E. Gilbert
8. Zhuo Fu

Citations in the corpus

• Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell Survival (2003, background): “Mice that contain inactivated PERK exhibit severe defects in the exocrine pancreas due to a high rate of secretory cell apoptosis (20, 44).”
• Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. (2001, background): “…in Development possibly similar to the proposed requirement for PERK in pancreatic -cell function in mice and humans (Dele-Upon growth in the presence of tunicamycin to induce ER stress, wild-type animals arrested at or prior to the pine et al., 2000; Scheuner et al., 2001; Harding et al., 2001).”
• β-Cell death during progression to diabetes (2001, background): “Another clue may come from Perk knockout mice, which develop diabetes at an early age owing to massive disappearance of β-cell”
• The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages (2003, background): “In addition, animals harbouring PERK mutations undergo rapid loss of specific secretory cell populations that are exposed to physiologically high levels of endoplasmic reticulum stres”
• An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. (2003, background): “…and humans lacking PERK activity experience progressive destruction of secretory cells with physiologically4 National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709 high levels of ER stress (Delepine et al., 2000; Harding et al., 2001; Zhang et al., 2002).”
• Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes (2007, background): “Using Eif2ak3-deficient mice [13], and in mice with a mutation in the EIF2A phosphorylation site (Ser51Ala) [14, 15], it has been demonstrated that beta cells are particularly sensitive to ER stress-induced dysfunction and death.”
• The PERK Eukaryotic Initiation Factor 2α Kinase Is Required for the Development of the Skeletal System, Postnatal Growth, and the Function and Viability of the Pancreas (2002, background): “Harding and coworkers (12) reported similar findings for insulin-secreting beta cells and acinar cells, but they did not report the loss of glucagon-secreting alpha FIG.”
• The role for endoplasmic reticulum stress in diabetes mellitus. (2008, background): “Mice with a PERK deletion cannot phosphorylate eIF2 and attenuate insulin translation, and they develop diabetes within a few weeks after birth due to progressive -cell loss (105, 106).”
• Pushing the limits of the scanning mechanism for initiation of translation (2002, background): “Initiation factor eIF2 plays a key role in translational control (Clemens, 2001; Dever, 2002) and mutations that perturb regulation of eIF2 have profound pathological consequences (Delépine et al., 2000; Han et al., 2001; Harding et al., 2001; Van der Knaap et al., 2002).”
• Measuring ER stress and the unfolded protein response using mammalian tissue culture system (2011, methodology): “Other available tools include PERK knockout mice and PERK knockout MEFs (Harding et al., 2001; Zhang et al., 2002, 2006).”
• Endoplasmic Reticulum Stress and the Unfolded Protein Response in Cellular Models of Parkinson's Disease (2002, methodology): “Cells lacking expression of PERK fail to phosphorylate eIF2 and to attenuate protein translation in response to ER stress (Harding et al., 2000a, 2001).”