Leads on the obesity-diabetes link

ﾩ Ed Hidden

The paper:

The finding:

The connection between obesity and type 2 diabetes is undeniable, but also unclear. In 2004, G￶khan 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.

The follow-up:

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 muscle. So is there a lineage to the effects, where events in the liver and adipose drive insulin resistance elsewhere, and if so, through what soluble mediators? That's a real key point that needs to be established."

The challenge:

Researchers have proposed other mechanisms to link obesity and diabetes, such as cytokines and lipid metabolism byproducts. "So are we talking about a conspiracy of several signaling pathways at once," asks Newgard, "or does one presage the other? That still needs to be sorted out."