Hypoglycemic Effect of Insulin-like Growth Factor II (IGF-II) Is Mediated Mainly through Insulin and/or IGF-I Receptor but not IGF-II Receptor

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Author(s)

    • Hizuka Naomi
    • Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College
    • Sakano Katsu-ichi
    • Department of Medicine, Molecular Biology Research Laboratory, Daiichi Pharmaceutical Co., Ltd.
    • Takano Kazue
    • Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College
    • Fukuda Izumi
    • Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College
    • Okubo Yumiko
    • Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College
    • Kazama Tomoko
    • Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College
    • Demura Hiroshi
    • Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College
    • Shizume Kazuo
    • Department of Medicine, Research Institute, The Foundation for Growth Science
    • Marumoto Yasumasa
    • Department of Medicine, Molecular Biology Research Laboratory, Daiichi Pharmaceutical Co., Ltd.

Abstract

Insulin-like growth factor-II (IGF-II) has an insulin-like effect <I>in vitro</I> and <I>in vivo</I>. Recently, mutants of IGF-II have been synthesized by the site-directed mutagenesis technique, and the structure determinants for the function of IGF-II have been studied. With the availability of the biosynthetic IGF-II and IGF-II mutants, we have investigated the hypoglycemic effect of IGF-II in normal rats and insulin resistant mice.<BR>When the IGF-II mutants with markedly decreased affinities for both insulin and IGF-I receptors were injected in normal rats, the blood glucose levels slightly decreased. However, when IGF-II mutant with slightly decreased affinities for both insulin and IGF-I receptors was injected, the blood glucose decreased to the same extent as with IGF-II.<BR>In insulin resistant mice, insulin did not decrease the blood glucose levels, but, the blood glucose levels decreased after IGF-I and IGF-II injection. The hypoglycemic effect of IGF-II was greater than that of IGF-I. The IGF-II mutant without affinity for IGF-II receptor but with affinities for both IGF-I and insulin receptors the same as IGF-II, caused hypoglycemia the same as IGF-I. However, the IGF-II mutant with markedly decreased affinities for both insulin and IGF-I receptors did not decrease blood glucose levels, and the IGF-II mutant with slightly decreased affinities for both insulin and IGF-II receptors slightly decreased blood glucose levels.<BR>These data indicate that the hypoglycemic effect of IGF-II is mediated mainly through insulin and/or IGF-I receptor but not IGF-II receptor. Furthermore, the data suggest that IGF-II might also be useful for the treatment of the insulin resistant status.

Journal

  • Clinical Pediatric Endocrinology

    Clinical Pediatric Endocrinology 5(Supple8), 77-83, 1996

    The Japanese Society for Pediatric Endocrinology

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