title: Delaying of insulin signal transduction in skeletal muscle cells by selenium compounds.
abstract: Supranutritional selenium (Se) intake and high serum Se levels have been associated epidemiologically with increased risk for type 2 diabetes, suggesting adverse effects of dietary Se compounds and/or antioxidant selenoenzymes on the sensitivity of target tissues for insulin. Here, we compared the capability of inorganic (sodium selenite and sodium selenate) and organic (selenomethionine and methylseleninic acid (MSeA)) Se compounds to interfere with insulin signaling in rat L6 myotubes, differentiated skeletal muscle cells. When applied at doses of 1 μM, only selenite and MSeA were capable of delaying insulin-induced phosphorylation of protein kinase B (Akt) and attenuating insulin-induced phosphorylation of forkhead box class O transcription factors FoxO1a and FoxO3. Insulin-stimulated glucose uptake was lowered by selenite and MSeA as well. Even though all tested Se compounds strongly stimulated expression/activity of the cellular selenoproteins glutathione peroxidase 1 and selenoprotein W, selenite and MSeA were the most efficiently utilized Se donors. Moreover, at doses of 1 μM, only selenite and MSeA had a significant inhibitory effect on generation of intracellular reactive oxygen species (ROS). These results suggest that the Se(IV) compounds selenite and MSeA may impair the insulin sensitivity of myocytes by influencing cellular redox homeostasis.
authors.affiliation: Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
authors.forename: Bodo
authors.initials: B
authors.lastname: Speckmann
authors.forename: Martin
authors.initials: M
authors.lastname: Heisler
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Holger
authors.initials: H
authors.lastname: Steinbrenner
mesh_terms: D000818:Animals; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000494:pharmacology*; D051140:Selenoproteins / Q000378:metabolism; D015398:Signal Transduction; D000071161:Forkhead Box Protein O1
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D007328:Insulin; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D051140:Selenoproteins; C499515:FOXO3 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1