title: Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat.
abstract: 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.
authors.affiliation: Institute of Physiology, Czech Academy of Sciences and the Center for Integrated Genomics, Prague 14220, Czech Republic. pravenec@biomed.cas.cz
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdová
authors.forename: Vladimir
authors.initials: V
authors.lastname: Landa
authors.forename: Václav
authors.initials: V
authors.lastname: Zidek
authors.forename: Petr
authors.initials: P
authors.lastname: Mlejnek
authors.forename: Petr
authors.initials: P
authors.lastname: Jansa
authors.forename: Jiaming
authors.initials: J
authors.lastname: Wang
authors.forename: Nianning
authors.initials: N
authors.lastname: Qi
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D006729:Hormones, Ectopic / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D020932:Nerve Growth Factor; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011506:Proteins; D051381:Rats; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins / Q000378:metabolism; D052243:Resistin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019076:Transgenes; D014280:Triglycerides / Q000378:metabolism
chemical_list: D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011994:Recombinant Proteins; D052243:Resistin; C499623:Retn protein, mouse; C499622:Retn protein, rat; C413576:Retnla protein, mouse; C486575:Retnla protein, rat; D014280:Triglycerides; D006003:Glycogen; D020932:Nerve Growth Factor; D005947:Glucose; D010100:Oxygen