Resistin, a cysteine-rich 12.5 kDa polypeptide, is an adipocytokine with a controversial history regarding its role in the pathogenesis of obesity-mediated insulin resistance and type 2 diabetes mellitus. Adipose tissue functions in the synthesis, storage, and mobilization of energy in the form of fat. These processes require continuous and efficient control so as to respond adequately to energy supply and demand. Adipose tissue is under hormonal control.
Resistin belongs to a new gene family of small, cysteine-rich secreted proteins, one member of which, named FIZZ, was originally detected in intestinal crypt cells and is induced in bronchial epithelial cells during inflammation. Other members of this family are resistin-like molecules called RELMs, which are found in the gastrointestinal tract. The cysteine residues function in the formation of disulfide bonds, resulting in hexamers, the form in which most resistin exists in mouse serum, with a small fraction occurring as a trimer. The latter is actually more physiologically active than the former. Its level is increased in diet-induced and genetic obesity, and therefore it is causally connected to obesity-associated insulin resistance. Resistin gene expression and protein secretion are markedly reduced by anti-diabetic TZDs. Resistin levels are increased in diet-induced obesity as well as in genetic models of obesity and insulin resistance. The effects of resistin administration and neutralization on glucose tolerance in vivo indicate that muscle, in addition to fat, may be a target for resistin; however, the molecular target of resistin is unknown.