Resistin: A Promising Therapeutic Target for the Management of Type 2 Diabetes Mellitus?

Type 2 diabetes mellitus (T2DM) represents an increasing epidemic in most of the countries throughout the Western world. One of the main determinants of such a situation is the growing incidence of overweight and obesity. However, the pathophysiological link between obesity and T2DM still remains unclear. The discovery of the circulating hormone resistin, which is produced mainly by adipocytes and appears to be increased in obesity and inflammation, seemed to clear up this connection. Some studies indicate that T2DM patients could have increased circulating concentrations of resistin, although these results need further confirmation. Seemingly, resistin opposes insulin action and impairs glucose tolerance and insulin sensitivity. In this sense, hyperinsulinemic clamp studies in rats support the notion that resistin selectively impairs insulin action in liver and increases hepatic glucose production. Furthermore, resistin knockout mice have evidenced that resistin has a physiological function in the maintenance of blood glucose during fasting through an increase of hepatic glucose output, which could be exacerbated in the obese state. These results support the notion that blockade of the biological effects of resistin might be a promising pharmaceutical target for the treatment of T2DM.