Does resistin resist insulin?

Diabetes remains one of the oldest diseases all over the world and is the major cause of morbidity and mortality in human populations. The pathology is a consequence of a lack of insulin or resistance to insulin, resulting in an increase in blood glucose levels. Resistance to insulin is an important risk factor in the industrial world and is often associated with obesity. Taking the proportions of an epidemic in the West, particularly USA, obesity is a consequence of an imbalance between energy intake and energy expenditure. Despite the strong clinical/pathological link between obesity and type-2 diabetes, the molecular link had remained a mystery. Recently, a unique signalling molecule was identified from mouse adipocytes. This molecule, termed as resistin (resistance to insulin), was found to be over expressed in the mouse model of obesity. Circulating resistin level decreased with the administration of antidiabetic drug, rosiglitazone. It was further shown that resistin levels increased in diet-induced and genetic forms of obesity (ob/ob and db/db). Insulinstimulated glucose uptake was greatly reduced upon treatment of 3T3 L1 adipose cells with purified recombinant resistin. Immuno-neutralization of resistin increased insulin sensitivity, whereas insulin resistance was seen upon treatment with purified resistin. This study attempted to categorically establish the involvement of resistin in mediating insulin resistance in diet-induced obesity. This exciting discovery, while trying to provide a molecular link between obesity and insulin resistance, generated several new questions. Is there an expression-related association of a resistin with pre-disposition to obesity and/or diabetes? What is the status of resistin in naturally obese human population?