Researchers probe chemical link to diabetes cure

A leading researcher at Harvard's School of Public Health has advanced research into the link between obesity and type 2 diabetes. Working with obese, diabetic mice, Gokhan S. Hotamisligil demonstrated that two chemicals--PBA (4-phenyl butyric acid) and TUDCA (taurine-conjugated derivative)--could restore healthy glucose levels and insulin activity. The cornerstone of that discovery was a hypothesis that the key to the obesity-diabetes connection might be found in the endoplasmic reticulum, or ER--a system of folded membranes and tubules in the cytoplasm of cells where proteins and lipids are manufactured, processed, and shipped around the cell. When unusual demands, such as excess fat, are put on the ER's capacity, the organelle starts failing, and the cell enters an emergency mode, emitting stress signals. The condition is called ER stress. Cellular inflammation, insulin resistance and diabetes result. TUDCA and PBA treatment also appeared to interfere with the storage of fat in the liver, significantly reducing the presence of fatty liver disease, a condition closely related to obesity and insulin resistance. One form of this disease--nonalcoholic steatohepatitis--is associated with inflammation and the creation of fibrous tissue, which can lead to cirrhosis.

"Already used safely in people for some disorders, these compounds and others like them may warrant clinical investigation into their effects on type 2 diabetes in humans," said Hotamisligil. "If these compounds work in humans as they do in experimental models, they could dramatically change the approaches to treat many components of metabolic syndrome."

- here's the release on the research project

PLUS: Researchers have found that the absence of ChREBP--carbohydrate response element binding protein--in mice keeps normally obese mice from becoming fat, lowers their blood triglycerides (a type of fat) and reduces the insulin resistance related to type 2 diabetes. Release

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