Injection of the insulin receptor alpha subunit increases blood glucose levels in mice |
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Authors: | Kanezaki Yoshiko Matsushima Rie Obata Toshiyuki Nakaya Yutaka Matsumoto Toshio Ebina Yousuke |
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Affiliation: | Division of Molecular Genetics, Institutes for Enzyme Research, The University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. |
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Abstract: | Using the expression vector of the truncated human insulin receptor (hIR), we have constructed a stable Chinese hamster ovary (CHO) cell line which secretes the His-tagged alpha subunit (insulin-binding domain) of hIR into medium. To examine characteristics of the His-tagged hIRalpha, we purified the protein secreted from the CHO cells. The His-tagged hIRalpha was glycosylated and processed a dimer. The molecule bound insulin with an affinity similar to that of the intact hIR. The His-tagged full length of hIR was autophosphorylated by insulin stimulation in CHO cells. Injection of the purified His-tagged hIRalpha into veins of mice increased in the concentration of blood glucose within 30 min. The intraperitoneal glucose tolerance test (ipGTT) done after injection of the purified His-tagged hIRalpha showed evidence of a marked hyperglycemia. These findings provide direct evidence that the presence of hIRalpha in the blood stream inhibits insulin actions by binding with plasma insulin. |
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Keywords: | Insulin receptor His-tagged α subunit Insulin binding Blood glucose concentration |
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