title: Genetic deletion of Trb3, the mammalian Drosophila tribbles homolog, displays normal hepatic insulin signaling and glucose homeostasis.
abstract: Trb3, a mammalian homolog of Drosophila tribbles, was proposed as a suppressor of Akt activity, predominantly in conditions of fasting and diabetes. Given these prior studies, we sought to determine whether Trb3 plays a major role in modulating hepatic insulin sensitivity. To answer this question, we produced mice in which a lacZ reporter was knocked into the locus containing the gene Trib3, resulting in a Trib3 null animal. Trib3 expression analyses demonstrated that the Trib3 is expressed in liver, adipose tissues, heart, kidney, lung, skin, small intestine, stomach, and denervated, but not normal, skeletal muscle. Trib3(-/-) mice are essentially identical to their wild-type littermates in overall appearance and body composition. Phenotypic analysis of Trib3(-/-) mice did not detect any alteration in serum glucose, insulin, or lipid levels; glucose or insulin tolerance; or energy metabolism. Studies in Trib3(-/-) hepatocytes revealed normal Akt and glycogen synthase kinase- 3beta phosphorylation patterns, glycogen levels, and expressions of key regulatory gluconeogenic and glycolytic genes. These data demonstrate that deletion of Trib3 has minimal effect on insulin-induced Akt activation in hepatic tissue, and, as such, they question any nonredundant role for Trb3 in the maintenance of glucose and energy homeostasis in mice.
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.
authors.forename: Haruka
authors.initials: H
authors.lastname: Okamoto
authors.forename: Esther
authors.initials: E
authors.lastname: Latres
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Karen
authors.initials: K
authors.lastname: Thabet
authors.forename: Andrew
authors.initials: A
authors.lastname: Murphy
authors.forename: David
authors.initials: D
authors.lastname: Valenzeula
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Trevor N
authors.initials: TN
authors.lastname: Stitt
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.forename: Mark W
authors.initials: MW
authors.lastname: Sleeman
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D022202:Chromosomes, Artificial, Bacterial; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008112:Liver Glycogen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D007328:Insulin; D008112:Liver Glycogen; C474830:TRB3 protein, mouse; D051058:Oncogene Protein v-akt; D000103:Acetyl-CoA Carboxylase; D005947:Glucose