U. Ozcan et al., "Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes," Science, 306:457-61, Oct. 15, 2004. (cited in 111 papers)
The connection between obesity and type 2 diabetes is undeniable, but also unclear. In 2004, Gökhan Hotamisligil's group at Harvard School of Public Health showed that obesity physically strains the endoplasmic reticulum (ER) of certain cell types, hyperactivating JNK, which then suppresses the cell's normal response to insulin.
This past August, Hotamisligil's group found that a class of drugs known as chemical chaperones relieve ER stress and can reverse type 2 diabetes in genetically obese and diabetic mice. "The effect was very impressive," says Chris Newgard at Duke University in Durham, NC.
The work ahead:
Newgard says the 2004 paper "demonstrated these pathways activated in the liver and adipose tissue, but interestingly not in the...