Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver

T. Kudo, M. Akiyama, K. Kuriyama, M. Sudo, T. Moriya, Shigenobu Shibata

    Research output: Contribution to journalArticle

    73 Citations (Scopus)

    Abstract

    Aims/hypothesis. An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides. Methods. Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits. Results. The db/db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression. Conclusions/interpretation. We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.

    Original languageEnglish
    Pages (from-to)1425-1436
    Number of pages12
    JournalDiabetologia
    Volume47
    Issue number8
    DOIs
    Publication statusPublished - 2004 Aug

    Fingerprint

    Gene Expression
    Liver
    Genes
    pioglitazone
    Locomotion
    Messenger RNA
    Insulin
    Triglycerides
    Glucose
    Plasminogen Activator Inhibitor 1
    Type 2 Diabetes Mellitus
    In Situ Hybridization
    Eating
    Myocardial Infarction
    Polymerase Chain Reaction
    Injections
    Therapeutics

    Keywords

    • Clock gene
    • db/db
    • Diabetes
    • Insulin
    • Liver
    • Peripheral oscillator
    • Restricted feeding

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver. / Kudo, T.; Akiyama, M.; Kuriyama, K.; Sudo, M.; Moriya, T.; Shibata, Shigenobu.

    In: Diabetologia, Vol. 47, No. 8, 08.2004, p. 1425-1436.

    Research output: Contribution to journalArticle

    Kudo, T. ; Akiyama, M. ; Kuriyama, K. ; Sudo, M. ; Moriya, T. ; Shibata, Shigenobu. / Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver. In: Diabetologia. 2004 ; Vol. 47, No. 8. pp. 1425-1436.
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    AU - Kudo, T.

    AU - Akiyama, M.

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    AU - Sudo, M.

    AU - Moriya, T.

    AU - Shibata, Shigenobu

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    AB - Aims/hypothesis. An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides. Methods. Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits. Results. The db/db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression. Conclusions/interpretation. We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.

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    KW - db/db

    KW - Diabetes

    KW - Insulin

    KW - Liver

    KW - Peripheral oscillator

    KW - Restricted feeding

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