title: Transgenic silkworms expressing human insulin receptors for evaluation of therapeutically active insulin receptor agonists.
abstract: We established a transgenic silkworm strain expressing the human insulin receptor (hIR) using the GAL4/UAS system. Administration of human insulin to transgenic silkworms expressing hIR decreased hemolymph sugar levels and facilitated Akt phosphorylation in the fat body. The decrease in hemolymph sugar levels induced by injection of human insulin in the transgenic silkworms expressing hIR was blocked by co-injection of wortmannin, a phosphoinositide 3-kinase inhibitor. Administration of bovine insulin, an hIR ligand, also effectively decreased sugar levels in the transgenic silkworms. These findings indicate that functional hIRs that respond to human insulin were successfully induced in the transgenic silkworms. We propose that the humanized silkworm expressing hIR is useful for in vivo evaluation of the therapeutic activities of insulin receptor agonists.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Miyaguchi
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Horie
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamamoto
authors.affiliation: Transgenic Silkworm Research Unit, National Institute of Agrobiological Sciences, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Tatematsu
authors.affiliation: Transgenic Silkworm Research Unit, National Institute of Agrobiological Sciences, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Keiro
authors.initials: K
authors.lastname: Uchino
authors.affiliation: Transgenic Silkworm Research Unit, National Institute of Agrobiological Sciences, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Transgenic Silkworm Research Unit, National Institute of Agrobiological Sciences, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sezutsu
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan. Electronic address: sekimizu@mol.f.y-tokyo.ac.jp.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D000595:Amino Acid Sequence; D000730:Androstadienes / Q000737:chemistry; D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000096:biosynthesis*; D012831:Bombyx / Q000235:genetics*; D002417:Cattle; D004195:Disease Models, Animal; D055808:Drug Discovery; D005947:Glucose / Q000032:analysis; D006458:Hemolymph / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D008024:Ligands; D008969:Molecular Sequence Data; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000819:agonists* / Q000096:biosynthesis*; D015398:Signal Transduction; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D015703:Antigens, CD; D007328:Insulin; D008024:Ligands; D000081082:Phosphoinositide-3 Kinase Inhibitors; C435941:INSR protein, human; D011972:Receptor, Insulin; D005947:Glucose; D000077191:Wortmannin
keywords: Drug discovery; Humanized silkworm; Hyperglycemia; Insulin; Transgenic