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

•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 in...

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Bibliographic Details
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
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Summary:•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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2014.10.143