The hormone resistin links obesity to diabetes

Abstract

Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage. Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear. Here we show that adipocytes secrete a unique signalling molecule, which we have named resistin (for resistance to insulin). Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity. Administration of anti-resistin antibody improves blood sugar and insulin action in mice with diet-induced obesity. Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action. Insulin-stimulated glucose uptake by adipocytes is enhanced by neutralization of resistin and is reduced by resistin treatment. Resistin is thus a hormone that potentially links obesity to diabetes.

Adipose Tissue as an Endocrine Organ

“…Resistin was initially identified in 2001 as a novel mRNA induced during adipocyte differentiation but down-regulated by TZDs in vitro and subsequently identified by other groups using independent methods (59 -61). In vivo studies in rodents confirmed adipose tissue-specific expression of resistin and down-regulation by TZDs (59). Resistin expression is 15-fold greater in visceral compared with sc adipose tissue in rodents (58).…”

“…Treatment of cultured adipocytes with recombinant resistin impairs insulin-stimulated glucose uptake whereas antiresistin antibodies prevent this effect (59). Similarly, in vivo treatment with recombinant resistin in rodents induces insulin resistance, whereas immunoneutralization of resistin has the opposite effect (59).…”

Cellular and molecular mechanisms in liver fibrogenesis

“…The biological role of resistin in humans is still controversial [49] and seems to differ for several aspects from what described in rodents. Indeed, in rodents resistin is up-regulated in dietinduced or genetic obesity [70] whereas in humans seems to have a role in sustaining inflammation, as shown by studies in which resistin is up-regulated in monocytes exposed to proinflammatory stimuli and in conditions of experimentally induced endotoxemia [71,72]. In relation to liver fibrogenesis, it has been shown that resistin expression during liver injury positively correlates with infiltration of inflammatory cells, which may represent the principal source of intrahepatic resistin [73].…”

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

“…Low levels of resistin are expressed in hepatocytes [18] and the production of resistin can be induced through a NF-kB-dependent cascade in human stellate cells and in a Hep G2 cell line [19]. The observation of the regulatory effect of resistin on carbohydrate metabolism in mice [20] initiated attempts to identify resistin-dependent mechanisms of fat deposition and insulin resistance in humans [18]. In fact, resistin has been described as a biomarker of insulin resistance and cirrhosis related to metabolic liver disease [21], but this has also been a matter of debate [22,23].…”