GLP-1 receptor activation improves β cell function and survival following induction of endoplasmic reticulum stress

Yusta, Bernardo; Baggio, Laurie L.; Estall, Jennifer L.; Koehler, Jacqueline A.; Holland, Diane T.; Liu, Hongyun; Pipeleers, Danny; Ling, Zhidong; Drucker, Daniel J.

doi:10.1016/j.cmet.2006.10.001

Cited by 398 publications

(334 citation statements)

References 92 publications

Supporting

Mentioning

312

Contrasting

Unclassified

Order By: Relevance

“…38 Similarly, incretin hormones, which promote survival of pancreatic b-cells, also induce GADD153/CHOP expression. 35 These data suggest that GADD153/CHOP can either promote or inhibit apoptosis. This speculation is further supported by the present study, which demonstrates that SV40 T-antigen-immortalized GADD153/CHOP-deficient mouse embryo fibroblasts are more resistant to apoptosis induced by tunicamycin, whereas sensitivity to thapsigargin-induced cell death is comparable between wild-type and GADD153/CHOPÀ/À cells.…”

Section: Figure 7 Continuedmentioning

confidence: 91%

“…34 Furthermore, the PKA pathway is involved in protection of pancreatic b-cells from ER stress mediated by GLP-1R agonists. 35 Finally, IGF-I-mediated antiapoptotic activity during serum starvation suggests involvement of PKC-dependent and MAPK-and PI3K-independent survival pathway(s). 36 Nevertheless, results of the present study demonstrate that none of the aforementioned pathways mediate the antiapoptotic activity of IGF-I during ER stress.…”

Section: Figure 7 Continuedmentioning

confidence: 99%

See 1 more Smart Citation

Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum

et al. 2008

View full text Add to dashboard Cite

Section: Figure 7 Continuedmentioning

confidence: 91%

Section: Figure 7 Continuedmentioning

confidence: 99%

Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum

et al. 2008

View full text Add to dashboard Cite

“…This could partially ameliorate the diabetic state if secretion resulting from the normal insulin allele could be better preserved. Glucagon-like peptide-1 receptor agonists and related agents could be useful in this regard (31,32).…”

Section: Discussionmentioning

confidence: 99%

Insulin gene mutations as a cause of permanent neonatal diabetes

Støy

Edghill

Flanagan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

511

478

View full text Add to dashboard Cite

We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with ␤ cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially ␤ cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of ␤ cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder.endoplasmic reticulum stress ͉ insulin biosynthesis ͉ disulfide bonds ͉ unfolded protein response

show abstract

“…6A). GLP-1, pioglitazone, and rapamycin are FDA-approved drugs and have been shown to confer protection against ER stress-mediated cell death (27,(31)(32)(33). Dantrolene is another FDA-approved drug clinically used for muscle spasticity and malignant hyperthermia (34).…”

Section: Significancementioning

confidence: 99%

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome

Kanekura

Hara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

137

168

View full text Add to dashboard Cite

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.Wolfram syndrome | endoplasmic reticulum | diabetes | neurodegeneration | treatment

show abstract

GLP-1 receptor activation improves β cell function and survival following induction of endoplasmic reticulum stress

Cited by 398 publications

References 92 publications

Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum

Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum

Insulin gene mutations as a cause of permanent neonatal diabetes

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome

Contact Info

Product

Resources

About