Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

By Umut Özcan, E. Yilmaz, Lale Özcan, M. Furuhashi, Éric Vaillancourt, R. O. Smith, Cem Z. Görgün, G. Hotamışlıgil. Science, 2006

2,444 citations recorded by the source corpus.

Subfields: Cell Biology, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/ef86a80b99f12e07033afab276d8e343cf9676e4

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Citations in the corpus

Lipid signalling in disease (2008, background): “Remarkably, orally active chemical chaperones that stabilize protein conformation and improve ER folding capacity can alleviate ER stress and can function as potent antidiabetic agents, restoring glucose homeostasis in mouse models of type 2 diabete”
Endoplasmic reticulum stress plays a central role in development of leptin resistance. (2009, background): “Indeed, in our experience, TUDCA acts as a much more powerful chemical chaperone when compared to PBA, as doses of TUDCA necessary for reducing ER stress in cellular systems (Ozcan et al., 2006) or as a leptin-sensitizing agent are much lower than for PBA.”
Mechanisms of insulin resistance in obesity (2013, background): “Inhibition of ER stress by chemical drugs is shown to improve insulin sensitivity in obese mice [103].”
Treatment of Obesity with Celastrol (2015, positive): “Use of Transcriptional Profiling to Identify Small-Molecule Leptin Sensitizers 4-PBA reduces ER stress, even in the absence of XBP1 (Ozcan et al., 2006), suggesting that each manipulation establishes ER homeostasis via independent pathways.”
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis (2010, background): “A beneficial effect for UDCA in the treatment of NASH has not been observed so far in various clinical trials,(111,112) An explanation for these discrepancies could be the fact that in vitro effects were observed using much higher UDCA concentrations than ever achievable in humans.(110) Studies usin”
Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains (2013, background): “Obesity, diet-induced ER stress, and UPR activation have been linked to insulin resistance (11, 41) and pancreatic β-cell failure (10) and may therefore have a role in the development of type 2 diabetes.”
The impact of the unfolded protein response on human disease (2012, background): “Treatment of obese and diabetic mice with the chemical chaperones PBA or taurine-conjugated ursodeoxycholic acid (TUDCA) alleviated ER stress–induced activation of c-JUN N-terminal kinase, corrected hyperglycemia, and improved systemic insulin sensitivity (Ozcan et al., 2006).”
Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress (2011, background): “Both have been used in humans for a variety of disorders and have beneficial effects in various mouse models of pathologic ER stres”
Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. (2018, background): “) for up to 30 days resolved hepatic steatosis in ob/ob mice(76).”