木内　謙一郎 （キノウチ　ケンイチロウ）

Kinouchi, Kenichiro

写真a

所属（所属キャンパス）

医学部 内科学教室（腎臓・内分泌・代謝） （信濃町）

職名

准教授
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学歴 【 表示 ／ 非表示 】

  • 2000年04月
    -
    2006年03月

    慶應義塾大学, 医学部

    大学, 卒業

  • 2008年04月
    -
    2011年03月

    慶應義塾大学, 医学部

    大学院, 卒業, 博士

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免許・資格 【 表示 ／ 非表示 】

  • 日本内科学会　内科認定医, 2009年

  • 日本内科学会　総合内科専門医, 2012年

  • 日本内分泌学会　内分泌代謝専門医, 2013年

  • 日本内分泌学会　内分泌代謝指導医, 2022年

  • 日本糖尿病学会　糖尿病専門医, 2023年

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研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 代謝、内分泌学

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  • Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice with Histone Acetylation in Dpp-4 Promoter

    Uto A., Miyashita K., Endo S., Sato M., Ryuzaki M., Kinouchi K., Mitsuishi M., Meguro S., Itoh H.

    Endocrinology (United States) （Endocrinology (United States)）  162 （ 12 ）  2021年12月

    ISSN  00137227

    　概要を見る

    Glucocorticoid causes hyperglycemia, which is common in patients with or without diabetes. Prolonged hyperglycemia can be experienced even after the discontinuation of glucocorticoid use. In the present study, we examined the time course of blood glucose level in hospital patients who received transient glucocorticoid treatment. In addition, the mechanism of prolonged hyperglycemia was investigated by using dexamethasone (Dexa)-treated mice and cultured cells. The blood glucose level in glucose tolerance tests, level of insulin and glucagon-like peptide 1 (GLP-1), and the activity of dipeptidyl peptidase 4 (DPP-4) were examined during and after Dexa loading in mice, with histone acetylation level of the promoter region. Mice showed prolonged hyperglycemia during and after transient Dexa loading accompanied by persistently lower blood GLP-1 level and higher activity of DPP-4. The expression level of Dpp-4 was increased in the mononuclear cells and the promoter region of Dpp-4 was hyperacetylated during and after the transient Dexa treatment. In vitro experiments also indicated development of histone hyperacetylation in the Dpp-4 promoter region during and after Dexa treatment. The upregulation of Dpp-4 in cultured cells was significantly inhibited by a histone acetyltransferase inhibitor. Moreover, the histone hyperacetylation induced by Dexa was reversible by treatment with a sirtuin histone deacetylase activator, nicotinamide mononucleotide. We identified persistent reduction in blood GLP-1 level with hyperglycemia during and after Dexa treatment in mice, associated with histone hyperacetylation of promoter region of Dpp-4. The results unveil a novel mechanism of glucocorticoid-induced hyperglycemia, and suggest therapeutic intervention through epigenetic modification of Dpp-4.

  • Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: A study in pigs

    Ichihara G., Katsumata Y., Moriyama H., Kitakata H., Hirai A., Momoi M., Ko S., Shinya Y., Kinouchi K., Kobayashi E., Sano M.

    Heliyon （Heliyon）  7 （ 11 ）  2021年11月

    ISSN  24058440

    　概要を見る

    Drinking hydrogen (H2)-rich water is a common way to consume H2. Although many studies have shown efficacy of drinking H2-rich water in neuropsychiatric and endocrine metabolic disorders, their authenticity has been questioned because none examined the associated pharmacokinetics of H2. Therefore, we performed the first study to investigate the pharmacokinetics of H2 in pigs given an H2-rich glucose solution with the aim to extrapolate the findings to humans. We inserted blood collection catheters into the jejunal and portal veins, suprahepatic inferior vena cava, and carotid artery of 4 female pigs aged 8 weeks. Then, within 2 min we infused 500 ml of either H2-rich or H2-free glucose solution into the jejunum via a percutaneous gastrostomy tube and measured changes in H2 concentration in venous and arterial blood over 120 min. After infusion of the H2-rich glucose solution, H2 concentration in the portal vein peaked at 0.05 mg/L and remained at more than 0.016 mg/L (H2 saturation level, 1%) after 1 h; it also increased after infusion of H2-free glucose solution but remained below 0.001 mg/L (H2 saturation level, 0.06%). We assume that H2 was subsequently metabolized in the liver or eliminated via the lungs because it was not detected in the carotid artery. In conclusion, drinking highly concentrated H2-rich solution within a short time is a good way to increase H2 concentration in portal blood and supply H2 to the liver.

  • Circadian rhythms in the tissue-specificity from metabolism to immunity: insights from omics studies

    Kinouchi K., Mikami Y., Kanai T., Itoh H.

    Molecular Aspects of Medicine （Molecular Aspects of Medicine）  80 2021年08月

    ISSN  00982997

    　概要を見る

    Creatures on earth have the capacity to preserve homeostasis in response to changing environments. The circadian clock enables organisms to adapt to daily predictable rhythms in surrounding conditions. In mammals, circadian clocks constitute hierarchical network, where the central pacemaker in hypothalamic suprachiasmatic nucleus (SCN) serves as a time-keeping machinery and governs peripheral clocks in every other organ through descending neural and humoral factors. The central clock in SCN is reset by light, whilst peripheral clocks are entrained by feeding-fasting rhythms, emphasizing the point that temporal patterns of nutrient availability specifies peripheral clock functions. Indeed, emerging evidence revealed various types of diets or timing of food intake reprogram circadian rhythms in a tissue specific manner. This advancement in understanding of mechanisms underlying tissue specific responsiveness of circadian oscillators to nutrients at the genomic and epigenomic levels is largely owing to employment of state-of-the-art technologies. Specifically, high-throughput transcriptome, proteome, and metabolome have provided insights into how genes, proteins, and metabolites behave over circadian cycles in a given tissue under a certain dietary condition in an unbiased fashion. Additionally, combinations with specialized types of sequencing such as nascent-seq and ribosomal profiling allow us to dissect how circadian rhythms are generated or obliterated at each step of gene regulation. Importantly, chromatin immunoprecipitation followed by deep sequencing methods provide chromatin landscape in terms of regulatory mechanisms of circadian gene expression. In this review, we outline recent discoveries on temporal genomic and epigenomic regulation of circadian rhythms, discussing entrainment of the circadian rhythms by feeding as a fundamental new comprehension of metabolism and immune response, and as a potential therapeutic strategy of metabolic and inflammatory diseases.

  • Combined Gene Expression and Chromatin Immunoprecipitation From a Single Mouse Hippocampus

    Helbling J.C., Kinouchi K., Trifilieff P., Sassone-Corsi P., Moisan M.P.

    Current Protocols （Current Protocols）  1 （ 2 ）  2021年02月

    　概要を見る

    All neuronal cells hold the same genetic information but vary by their structural and functional plasticity depending on the brain area and environmental influences. Such variability involves specific gene regulation, which is driven by transcription factors (TFs). In the field of neuroscience, epigenetics is the main mechanism that has been investigated to understand the dynamic modulation of gene expression by behavioral responses, stress responses, memory processes, etc. Nowadays, gene expression analyzed by real-time quantitative PCR and TF binding estimated by chromatin immunoprecipitation (ChIP) enables one to dissect this regulation. Because of the wide range of transgenic models, as well as cost-effective aspects, mouse models are widely used neuroscience. Thus, we have set up a protocol that allows extraction of both RNA for gene expression analysis and chromatin for ChIP experiment from a single mouse hippocampus. Using such protocols, information regarding gene expression and regulatory molecular mechanisms from the same animal can be integrated and correlated with neurobiological and behavioral outcomes. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Hippocampus isolation from mouse brain. Basic Protocol 2: RNA extraction and gene expression analysis from a mouse half hippocampus. Basic Protocol 3: ChIP from one hemisphere side mouse hippocampus.

  • S-adenosyl-l-homocysteine hydrolase links methionine metabolism to the circadian clock and chromatin remodeling

    Greco C.M., Cervantes M., Fustin J.M., Ito K., Ceglia N., Samad M., Shi J., Koronowski K.B., Forne I., Ranjit S., Gaucher J., Kinouchi K., Kojima R., Gratton E., Li W., Baldi P., Imhof A., Okamura H., Sassone-Corsi P.

    Science Advances （Science Advances）  6 （ 51 ）  2020年12月

    　概要を見る

    Circadian gene expression driven by transcription activators CLOCK and BMAL1 is intimately associated with dynamic chromatin remodeling. However, how cellular metabolism directs circadian chromatin remodeling is virtually unexplored. We report that the S-adenosylhomocysteine (SAH) hydrolyzing enzyme adenosylhomocysteinase (AHCY) cyclically associates to CLOCK-BMAL1 at chromatin sites and promotes circadian transcriptional activity. SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases, and timely hydrolysis of SAH by AHCY is critical to sustain methylation reactions. We show that AHCY is essential for cyclic H3K4 trimethylation, genome-wide recruitment of BMAL1 to chromatin, and subsequent circadian transcription. Depletion or targeted pharmacological inhibition of AHCY in mammalian cells markedly decreases the amplitude of circadian gene expression. In mice, pharmacological inhibition of AHCY in the hypothalamus alters circadian locomotor activity and rhythmic transcription within the suprachiasmatic nucleus. These results reveal a previously unappreciated connection between cellular metabolism, chromatin dynamics, and circadian regulation.

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KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 腸管Tリンパ球における体内時計と増殖代謝

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 木内　謙一郎, 基盤研究（Ｃ）, 補助金,  研究代表者

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担当授業科目 【 表示 ／ 非表示 】

  • 慢性期病態学各論

    2025年度

  • 内科学（腎臓・内分泌・代謝）講義

    2025年度

  • 腎臓・内分泌・代謝内科学臨床実習

    2025年度

  • 内科学（腎臓・内分泌・代謝）臨床実習

    2025年度

  • 医化学

    2025年度

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