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健康増進医学(協力)健康スポーツ医学

研究室概要

インスリン抵抗性は、肥満症、糖尿病、高血圧症で代表される生活習慣病の主要病態であるとともに、老化の原因でもあると考えられている。我々の研究室は、インスリン抵抗性の発症メカニズムとその対策を明らかにし、生活習慣病の発症防止、進展阻止に貢献することを目指している。特に、運動と栄養療法による予防的な介入に着目し、ヒトを対象とした研究、in vivo の 動物実験、分子生物学的検討などの手法で検討している。近年は、中枢における糖・エネルギー代謝調節機構に関する研究も開始している。

研究プロジェクト

1. インスリン抵抗性に対する基礎的、臨床的検討

私たちは、インスリン抵抗性の影響を、糖代謝に加え、骨格筋や脳に着目し、検討している。骨格筋は、糖代謝の主な制御臓器であるとともに、身体機能にとって必須な臓器である。超高齢社会を迎え、加齢性骨格筋減少（サルコペニア）が原因となる身体的虚弱性（フレイル）をともなう高齢者が増加し、そのQOLを左右する臓器として医学的にも注目されるようになった。さらに、脳に起こる慢性炎症は、認知機能低下との関連が示唆されている。老化との関連が強いサルコペニアや認知症の病態にインスリン抵抗性は深くかかわっており、運動、栄養による予防・治療が期待されている。このようなことを背景とし、糖代謝、骨格筋の質・量、脳慢性炎症に及ぼす効果を指標に、身体トレーニング法と栄養介入による適切なインスリン抵抗性制御方法を明らかにする。

2. 糖・エネルギーバランスの調節機構

エネルギーバランスは脳（中枢）によって調節されている。生活習慣病の原因である肥満症は、既にパンデミックレベルで蔓延しているにも関わらず有効な内科的治療法は未だ確立しておらず、発症機序の解明および治療法の確立が期待される。我々は高脂肪食摂取による糖・エネルギー代謝異常に加え、中枢による糖代謝調節機構について研究しており、特にインスリン、レプチンおよび炎症の調節因子であるprotein tyrosine phosphatase 1B（PTP1B）に着目し、様々な遺伝子改変マウスを用いて糖・エネルギーバランスの調節機構の解明を進めている。

教員

構成員名役職所属
小池 晃彦 教授 健康スポーツ医学
坂野 僚一 准教授 健康スポーツ医学

研究実績

  • 2019年
    1. 1. M. Hioki, N. Kanehira, T. Koike, A. Saito. H. Takahashi, K, Shimaoka, H. Sakakibara, H. Oshida, Y., H. Akima: Relationship between Physical activity and intracellular lipid content is different between young and older adults. Eur J Appl Physiol 2019, 119:113-122
    2. 2. Kano M, Suga H, Ishihara T, Sakakibara M, Soen M, Yamada T, Ozaki H, Mitsumoto K, Kasai T, Sugiyama M, Onoue T, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Banno R, Arima H: Tanycyte-like cells derived from mouse embryonic stem culture show hypothalamic neural stem/progenitor cell functions. Endocrinology. 2019, en.2019-00105.
    3. 3. Yoshiko A, Natsume Y, Mariko T, Hayashi T, Umegaki H, Yoshida Y, Cheng XW, Kuzuya M, Ishida K, Koike T, Oshida Y, Akima H. Higher and lower muscle echo intensity in elderly individuals is distinguished by muscle size, physical performance and daily physical activity. Ultrasound Med Biol.2019, https://doi.org/10.1016/j.ultrasmedbio.2019.05.029
    4. 4. Yoshiko A, Kaji T, Sugiyama H, Koike T, Oshida Y, Akima H. Twenty-four months’ resistance and endurance training improves muscle size and physical functions but not muscle quality in older adults requiring long-term care. J Nutr Health Aging. 2019, 23(6):564-570
  • 2018年
    1. 1. Siriguleng, Koike T, Natsume Y, Iwama S, Oshida Y: Effect of prior chronic aerobic exercise on overload-induced skeletal muscle hypertrophy in mice. Physiol Res. 2018, 67(5):765-775
    2. 2. Tochiya M, Hagiwara D, Azuma Y, Miyata T, Morishita Y, Suga H, Onoue T, Tsunekawa T, Takagi H, Ito Y, Iwama S, Goto M, Banno R, Arima H: Chemical chaperone 4-phenylbutylate reduces mutant protein accumulation in the endoplasmic reticulum of arginine vasopressin neurons in a mouse model for familial neurohypophysial diabetes insipidus. Neurosci Lett. 2018, 682:50-55.
    3. 3. Kobayashi T, Iwama S, Yasuda Y, Okada N, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Yokota K, Hase T, Morise M, Hashimoto N, Ando M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H: Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. J Endocr Soc. 2018, 2(3):241-251.
    4. 4. Ogawa K, Suga H, Ozone C, Sakakibara M, Yamada T, Kano M, Mitsumoto K, Kasai T, Kodani Y, Nagasaki H, Yamamoto N, Hagiwara D, Goto M, Banno R, Sugimura Y, Arima H: Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors. Sci Rep. 2018, 8(1):3615.
    5. 5. Yasuda Y, Iwama S, Kiyota A, Izumida H, Nakashima K, Iwata N, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Enomoto A, Takahashi M, Arima H, Sugimura Y: Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis. J Pathol. 2018, 244(4):469-478.
    6. 6. Takeda A, Koike T, Urata S, Ishida T, Oshida Y. Effect of acupuncture at the Shenshu point on the bones of overiectomized rats. Journal of Traditional Chinese Medicine. 2018, 38(1):54-60
    7. 7. Katayama K, Smith JR, Goto K, Shimizu K, Saito M, Ishida K, Koike T, Iwase S, Harms CA. Elevated sympathetic vasomotor outflow in response to increased inspiratory muscle activity during exercise is less in young women compared with men. 2018 Exp Physiol 103(4):570-580
    8. 8. Yoshiko A, Kaji T, Sugiyama H, Koike T, Oshida Y, Akima H. Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women. Eur. J. Appl. Physiol. 2018, 118(7):1385-1395
    9. 9. Yoshiko A, Yamauchi K, Kato T, Ishida K, Koike T, Oshida Y, Akima H. Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in thigh and calf. Skeletal　Radiol 47(11):1541-1549
    10. 10. Yoshiko A, Tomita A, Ando R, Ogawa M, Kondo S, Saito A, Tanaka NI, Koike T, Oshida Y, Akima H. 2018 Effects of 10-week walking and walking with home-based resistance training on muscle quality, muscle size, and physical functional tests in healthy older individuals. 2018, Eur Rev Aging Phys Act 15(13)
    11. 11. Yoshiko A, Tomita A, Ando R, Ogawa M, Kondo S, Saito A, Tanaka NI, Koike T, Oshida Y, Akima H. Effects of 10-week walking and walking with home-based resistance training on muscle quality, muscle size, and physical functional tests in healthy older individuals. 2018, Eur Rev Aging Phys Act 15(13)
  • 2017年
    1. Yoshiko A, Hioki M, Kanehira N, Shimaoka K, Koike T, Sakakibara H, Oshida Y, Akima H:Three-dimensional comparison of intramuscular fat content between young and old adults. BMC Medical Imaging 2017;17(12): DOI 10.1186/s12880-017-0185-9
    2. Sugiyama M, Banno R, Mizoguchi A, Tominaga T, Tsunekawa T, Onoue T, Hagiwara D, Ito Y, Morishita Y, Iwama S, Goto M, Suga H, Arima H:PTP1B deficiency improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under high-fat diet conditions. Biochem Biophys Res Commun. 2017;488(1):116-121
    3. Muraoka Y, Iwama S, Arima H:Normalization of bilateral adrenal gland enlargement after treatment for cryptococcosis. Case Rep Endocrinol. 2017;2017:1543149
    4. Sakurai K, Yamashita R, Niituma S, Iwama S, Sugimura Y, Arihara Z, Takahashi K:Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes insipidus in the third trimester of pregnancy. Endocr J. 2017;doi:10.1507/endocrj.EJ17-0028 [Epub ahead of print]
    5. Tsunekawa T, Banno R, Mizoguchi A, Sugiyama M, Tominaga T, Onoue T, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Sugimura Y, Arima H:Deficiency of PTP1B attenuates hypothalamic inflammation via activation of the JAK2-STAT3 pathway in microglia. EBioMedicine 2017;16:172-183
    6. Izumida H, Takagi H, Fujisawa H, Iwata N, Nakashima K, Takeuchi S, Iwama S, Namba T, Komatu Y, Kaibuchi K, Oiso Y, Arima H, Sugimura Y:NMDA receptor antagonist prevents cell death in the hippocampal dentate gyrus induced by hyponatremia accompanying adrenal insufficiency in rats. Exp Neurol. 2017;287(Pt 1):65-74. doi: 10.1016/j.expneurol.2016.08.007
  • 2016年
    1. Akima H, Hioki M, Yoshiko A, Koike T, Sakakibara H, Takahashi H, Oshida Y: Intramuscular adipose tissue determined by T1-weighted MRI at 3T primarily reflects extramyocellular lipids. Magn Reson Imaging 2016;34:397-403
    2. Hioki M, Kanehira N, Koike T, Saito A, Takahashi H, Shimaoka K, Sakakibara H, Oshida Y, Akima H: Associations of intramyocellular lipid in vastus lateralis and biceps femoris with blood free fatty acid and muscle strength differ between young and elderly adults. Clin Physiol Funct Imaging 2016;36:457-463
    3. Katayama K, Ishida K, Saito M, Koike T, Ogoh S: Hypoxia attenuates cardiopulmonary reflex control of sympathetic nerve activity during mild dynamic leg exercise. Exp Physiol 2016;101:377-386
    4. Kusunoki M, Natsume Y, Sato D, Tsutsui H, Miyata T, Tsutsumi K, Suga T, Oshida T:Luseogliflozin, a sodium glucose co-transporter 2 inhibitor, alleviates hepatic impairment in Japanese patients with type 2 diabetes. Drug Research 2016;66(11):603-606
    5. Inoue A, Cheng XW, Huang Z, Kikuchi R, Hu L, Jiang H, Sasaki T, Piao L, Wu Hongxian , Li X, Zhao G, Zhu E, Lei Y, Itakura K, Bando Y, Oshida Y, Koike T, Kuzuya M:Exercise restores muscle stem cell mobilization and regenerative capacity and muscle metabolic alterations via adiponectin/adipoR1 activation in SAMP10 mice. Journal of Cachexia, Sarcopenia and Muscle 2016;DOI:10.1002/jcsm.12166
    6. Iwata N, Iwama S, Sugimura Y, Yasuda Y, Nakashima K, Takeuchi S, Hagiwara D, Ito Y, Suga H, Goto M, Banno R, Caturegli P, Koike T, Oshida Y, Arima H:Anti-pituitary antibodies against corcicotrophsin IgG4-related hypophysitis. Pituitary 2016;DOI:10.1007/s11102-016-0780-8
    7. Takeuchi S, Iwama S, Takagi H, Kiyota A, Nakashima K, Izumida H, Fujisawa H, Iwata N, Suga H, Watanabe T, Kaibuchi K, Oiso Y, Arima H, Sugimura Y:Tomosyn negatively regulates arginine vasopressin secretion in embryonic stem cell-derived neurons. PLoS One 2016;11(10):e0164544. doi: 10.1371/journal.pone.0164544
    8. Fujisawa H, Sugimura Y, Takagi H, Mizoguchi H, Takeuchi H, Izumida H, Nakashima K, Ochiai H, Takeuchi S, Kiyota A, Fukumoto K, Iwama S, Takagishi Y, Hayashi Y, Arima H, Komatsu Y, Murata Y, Oiso Y:Chronic hyponatremia causes neurologic and psychologic impairments. J Am Soc Nephrol. 2016;27(3):766-80
    9. 岩間信太郎:スポーツ頭部外傷に伴う下垂体機能低下症. 総合保健体育科学 2016;39(1):1-4
    10. 石黒洋、中原久美子、宮田祐子、長尾杏子、千藤ますみ、市橋淳、木村千春、小池晃彦、山本明子、岩間信太郎、押田芳治:名古屋大学における健診データ自動収集システムについて. CAMPUS HEALTH. 2016;53(2):33-36
  • 2015年
    1. Akima H, Yoshiko A, Hioki M, Kanehira N, Shimaoka K, Koike T, Sakakibara H, Oshida Y: Skeletal muscle size is a major predictor of intramuscular fat content regardless of age. Eur J Appl Physiol 2015;115:1627-1635
    2. Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H, Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y: Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis. J Clin Endocrinol Metab 2015;100:E946-954
    3. Katayama K, Itoh Y, Saito M, Koike T, Ishida K: Sympathetic vasomotor outflow and blood pressure increase during exercise with expiratory resistance. Physiological reports 2015;3
    4. Takagi Y, Kinoshita K, Ozaki N, Seino Y, Murata Y, Oshida Y, Hayashi Y: Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity. PLoS One 2015;10:e0138322
  • 2014年
    1. Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P: Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med 2014;6:230ra245
    2. Jiang H, Cheng XW, Shi GP, Hu L, Inoue A, Yamamura Y, Wu H, Takeshita K, Li X, Huang Z, Song H, Asai M, Hao CN, Unno K, Koike T, Oshida Y, Okumura K, Murohara T, Kuzuya M: Cathepsin K-mediated Notch1 activation contributes to neovascularization in response to hypoxia. Nature communications 2014;5:3838
    3. Katayama K, Ishida K, Saito M, Koike T, Hirasawa A, Ogoh S: Enhanced muscle pump during mild dynamic leg exercise inhibits sympathetic vasomotor outflow. Physiological reports 2014;2
    4. Kinoshita K, Ozaki N, Takagi Y, Murata Y, Oshida Y, Hayashi Y: Glucagon is essential for adaptive thermogenesis in brown adipose tissue. Endocrinology 2014;155:3484-3492
  • 2013年
    1. Iwama S, Welt CK, Romero CJ, Radovick S, Caturegli P: Isolated prolactin deficiency associated with serum autoantibodies against prolactin-secreting cells. J Clin Endocrinol Metab 2013;98:3920-3925
    2. Iwamoto E, Katayama K, Yamashita S, Oshida Y, Ishida K: Retrograde blood flow in the inactive limb is enhanced during constant-load leg cycling in hypoxia. Eur J Appl Physiol 2013;113:2565-2575
    3. Katayama K, Yamashita S, Ishida K, Iwamoto E, Koike T, Saito M: Hypoxic effects on sympathetic vasomotor outflow and blood pressure during exercise with inspiratory resistance. Am J Physiol Regul Integr Comp Physiol 2013;304:R374-382
  • 2012年
    1. Iwama S, De Remigis A, Bishop JA, Kimura HJ, Caturegli P: Hurthle cells predict hypothyroidism in interferon-gamma transgenic mice of different genetic backgrounds. Endocrinology 2012;153:4059-4066
    2. Iwamoto E, Katayama K, Oshida Y, Ishida K: Hypoxia augments oscillatory blood flow in brachial artery during leg cycling. Med Sci Sports Exerc 2012;44:1035-1042
    3. Katayama K, Iwamoto E, Ishida K, Koike T, Saito M: Inspiratory muscle fatigue increases sympathetic vasomotor outflow and blood pressure during submaximal exercise. Am J Physiol Regul Integr Comp Physiol 2012;302:R1167-1175
    4. Li P, Koike T, Jiang HY, Wang ZH, Kawata Y, Oshida Y: Acute treatment with candesartan cilexetil, an angiotensin II type 1 receptor blocker, improves insulin sensitivity in high-fructose-diet-fed rats. Horm Metab Res 2012;44:286-290
    5. Wang Z, Koike T, Li P, Jiang H, Natsume Y, Mu L, Chen T, Oshida Y: Effects of angiotensin II AT1 receptor inhibition and exercise training on insulin action in rats on high-fat diet. Life Sci 2012;90:322-327

研究キーワード

インスリン抵抗性、身体トレーニング、栄養、骨格筋、糖代謝、糖尿病、肥満症

健康スポーツ医学 独自ホームページ

大学院生募集

本研究室に興味のある方は、遠慮せずにどんどん見学にいらしてください。研究室の見学、教員･大学院生とのコンタクトを希望される方は、事前に koike@htc.nagoya-u.ac.jp （小池 晃彦）までメールにてご連絡ください。