Physiology Resistin' the Effects of Insulin

Type II diabetes patients are often obese and, usually, their hyperglycemic condition is refractory to insulin administration. Some of the proteins responsible for promoting this "insulin resistance" have been identified; however, our knowledge of the pathways involved is far from complete. Steppan et al. have now identified and characterized a new protein termed resistin that may bridge obesity and diabetes. Resistin was identified through a screening assay designed to identify genes whose expression was decreased in adipocytes treated with thiazolidinediones, a new class of antidiabetes drugs that target peroxisome proliferator-activated receptor- (PPAR-). Resistin protein levels were greatly reduced in thiazolidinedione-treated adipocytes and in similarly treated mice, but resistin protein levels were higher in obese (ob/ob) and diabetic (db/db) mice and in mice fed a high-fat diet. High levels of resistin correlated positively with insulin resistance and decreased glucose transport. Hyperglycemic, insulin-resistant mice injected with resistin antibodies exhibited lower serum glucose levels. These data suggest that resistin helps control adipocyte sensitivity to insulin and may be a link between obesity and diabetes. A News & Views article by Flier discusses the possible role of resistin in diabetes, in the context of other proteins known to affect insulin resistance.

C. M. Steppan, S. T. Bailey, S. Bhat, E. J. Brown, R. R. Banerjee, C. M. Wright, H. R. Patel, R. S. Ahima, M. A. Lazar, The hormone resistin links obesity to diabetes. Nature 409, 307-312 (2001). [Online Journal]

J. S. Flier, The missing link with obesity? Nature 409, 292-293 (2001). [Online Journal]