Increased serum levels of resistin, a molecule secreted by fat cells, have been proposed as a possible mechanistic link between obesity and insulin resistance. To further investigate the effects of resistin on glucose metabolism, we derived a novel transgenic strain of spontaneously hypertensive rats expressing the mouse resistin gene under the control of the fat-specific aP2 promoter and also performed in vitro studies of the effects of recombinant resistin on glucose metabolism in isolated skeletal muscle. Expression of the resistin transgene was detected by Northern blot analysis in adipose tissue and by real-time PCR in skeletal muscle and was associated with increased serum fatty acids and muscle triglycerides, impaired skeletal muscle glucose metabolism, and glucose intolerance in the absence of any changes in serum resistin concentrations. In skeletal muscle isolated from non-transgenic spontaneously hypertensive rats, in vitro incubation with recombinant resistin significantly inhibited insulin-stimulated glycogenesis and reduced glucose oxidation. These findings raise the possibility that autocrine effects of resistin in adipocytes, leading to release of other prodiabetic effector molecules from fat and/or paracrine actions of resistin secreted by adipocytes embedded within skeletal muscle, may contribute to the pathogenesis of disordered skeletal muscle glucose metabolism and impaired glucose tolerance.

Institute of Physiology Czech Academy of Sciences and the Center for Integrated Genomics Prague 14220 Czech Republic

References provided by Crossref.org

Beneficial Effect of Fenofibrate in Combination with Silymarin on Parameters of Hereditary Hypertriglyceridemia-Induced Disorders in an Animal Model of Metabolic Syndrome

Genetic Complementation of ATP Synthase Deficiency Due to Dysfunction of TMEM70 Assembly Factor in Rat

Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats

Age-related autocrine diabetogenic effects of transgenic resistin in spontaneously hypertensive rats: gene expression profile analysis

n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet

Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains