title: Glucose, dexamethasone, and the unfolded protein response regulate TRB3 mRNA expression in 3T3-L1 adipocytes and L6 myotubes.
abstract: Tribbles 3 (TRB3) is a recently recognized atypical inactive kinase that negatively regulates Akt activity in hepatocytes, resulting in insulin resistance. Recent reports link TRB3 to nutrient sensing and regulation of cell survival under stressful conditions. We studied the regulation of TRB3 by glucose, insulin, dexamethasone (Dex), and the unfolded protein response (UPR) in 3T3-L1 adipocytes and in L6 myotubes. In 3T3-L1 adipocytes, incubation in high glucose with insulin did not increase TRB3 mRNA expression. Rather, TRB3 mRNA increased fourfold with glucose deprivation and two- to threefold after incubation with tunicamcyin (an inducer of the UPR). Incubation of cells in no glucose or in tunicamcyin stimulated the expression of CCAAT/enhancer-binding protein homologous protein. In L6 myotubes, absent or low glucose induced TRB3 mRNA expression by six- and twofold, respectively. The addition of Dex to 5 mM glucose increased TRB3 mRNA expression twofold in 3T3-L1 adipocytes but decreased it 16% in L6 cells. In conclusion, TRB3 is not the mediator of high glucose or glucocorticoid-induced insulin resistance in 3T3-L1 adipocytes or L6 myotubes. TRB3 is induced by glucose deprivation in both cell types as a part of the UPR, where it may be involved in regulation of cell survival in response to glucose depletion.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Sherif Z
authors.initials: SZ
authors.lastname: Yacoub Wasef
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Robinson
authors.forename: Mary N
authors.initials: MN
authors.lastname: Berkaw
authors.forename: Maria G
authors.initials: MG
authors.lastname: Buse
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D017510:Protein Folding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000096:biosynthesis
chemical_list: D018797:Cell Cycle Proteins; D003470:Culture Media; C497250:Ddit3 protein, mouse; D012333:RNA, Messenger; C474830:TRB3 protein, mouse; D051742:Transcription Factor CHOP; D003907:Dexamethasone; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose