Obesity triggers stress in the endoplasmic reticulum (ER), a network of intracellular membranes involved in protein folding and trafficking. That ER stress in turn disrupts insulin signaling. Özcan et al. investigated whether a class of small-molecule drugs that normalize ER function, called "chemical chaperones," might have therapeutic benefits in type 2 diabetes. These drugs were found to correct hyperglycemia and restore insulin sensitivity in genetically obese and diabetic mice, suggesting that they merit further study as a potential therapy for human diabetes.
U. Özcan, E. Yilmaz, L. Özcan, M. Furuhashi, E. Vaillancourt, R. O. Smith, C. Z. Görgün, G. S. Hotamisligil, Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313, 1137-1140 (2006). [Abstract] [Full Text]