Reduced Carnitine Level Causes Death from Hypoglycemia: Possible Involvement of Suppression of Hypothalamic Orexin Expression During Weaning Period

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  • KUWAJIMA Masamichi
    Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School
  • FUJIHARA Hiroaki
    Department of Physiology, School of Medicine, University of Occupational and Environmental Health
  • SEI Hiroyoshi
    Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School
  • UMEHARA Asako
    Department of Human Life Science, Tokushima Bunri University
  • SEI Masako
    Department of Human Genetics and Public Health, Institute of Health Biosciences, The University of Tokushima Graduate School
  • TSUDA Tomi T.
    Department of Human Life Science, Tokushima Bunri University
  • SUKENO Akiko
    Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School
  • OKAMOTO Tatsuya
    Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School
  • INUBUSHI Akiko
    Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School
  • UETA Yoichi
    Department of Physiology, School of Medicine, University of Occupational and Environmental Health
  • DOI Toshio
    Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School
  • KIDO Hiroshi
    Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima Graduate School

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Abstract

The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.<br>

Journal

  • Endocrine Journal

    Endocrine Journal 54 (6), 911-925, 2007

    The Japan Endocrine Society

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