Transgenic silkworms expressing human insulin receptors for evaluation of therapeutically active insulin receptor agonists

• Published in: Biochemical and biophysical research communications 2014-12, Vol.455 (3-4), p.159-164
• Main Authors: Matsumoto, Yasuhiko, Ishii, Masaki, Ishii, Kenichi, Miyaguchi, Wataru, Horie, Ryo, Inagaki, Yoshinori, Hamamoto, Hiroshi, Tatematsu, Ken-ichiro, Uchino, Keiro, Tamura, Toshiki, Sezutsu, Hideki, Sekimizu, Kazuhisa
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Androstadienes - chemistry; Animals; Animals, Genetically Modified; Antigens, CD - biosynthesis; Bombyx - genetics; Bombyx mori; Cattle; Disease Models, Animal; Drug Discovery; Glucose - analysis; Hemolymph - drug effects; Humanized silkworm; Humans; Hyperglycemia; Insulin; Insulin - chemistry; Ligands; Molecular Sequence Data; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphorylation; Receptor, Insulin - agonists; Receptor, Insulin - biosynthesis; Signal Transduction; Transgenic
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.10.143

•We generated transgenic silkworms expressing the human insulin receptor (hIR).•Human insulin decreases hemolymph sugar levels in silkworms expressing hIR.•Human insulin activates the insulin-signaling pathway in silkworms expressing hIR.•The humanized transgenic silkworm is useful for evaluating insulin receptor agonists. 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.