研究室紹介LABORATORY

健康スポーツ医学

KEYWORDS

  • 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

HEAD

小池 晃彦

教授

研究者総覧

CONTACT

Email med◎t.mail.nagoya-u.ac.jp（送信の際は◎を@に変更してください）

OUTLINE

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。

RESEARCH PROJECTS

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。

BIBLIOGRAPHY

2025
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2024
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  2. Sasaki T, Sugiyama M, Kuno M, Miyata T, Kobayashi T, Yasuda Y, Onoue T, Takagi H, Hagiwara D, Iwama S, Suga H, Banno R, Arima H: Voluntary exercise suppresses inflammation and improves insulin resistance in the arcuate nucleus and ventral tegmental area in mice on a high-fat diet. Physiol Behav. 2024 Dec 1;287:114703. doi: 10.1016/j.physbeh.2024.114703.
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  5. Yamagami A, Iwama S, Kobayashi T, Zhou X, Yasuda Y, Okuji T, Ito M, Izuchi T, Ando M, Onoue T, Miyata T, Sugiyama M, Hagiwara D, Suga H, Banno R, Arima H: Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade. Endocr J. 2024 May 23;71(5):515-526. doi: 10.1507/endocrj.EJ23-0480.
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  8. Kobayashi T, Iwama S, Yamagami A, Izuchi T, Suzuki K, Otake K, Yasuda Y, Ando M, Onoue T, Miyata T, Sugiyama M, Hagiwara D, Suga H, Banno R, Hase T, Nishio N, Mori S, Shimokata T, Sano T, Niimi K, Yoshikawa N, Akamatsu S, Ando Y, Akiyama M, Sone M, Ishii M, Arima H: Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study. Cancer Immunol Immunother. 2024 Jun 4;73(8):146. doi: 10.1007/s00262-024-03733-2.
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2023
  1. Ito M, Iwama S, Sugiyama D, Yasuda Y, Okuji T, Kobayashi T, Zhou X, Yamagami A, Onoue T, Miyata T, Sugiyama M, Hagiwara D, Suga H, Banno R, Nishikawa H, Arima H: Anti-tumor effects of anti-programmed cell death-1 antibody treatment are attenuated in streptozotocin-induced diabetic mice. Sci Rep. 2023 Apr 12;13(1):5939. doi: 10.1038/s41598-023-33049-7.
  2. Kawaguchi Y, Hagiwara D, Tsumura T, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Yasuda Y, Iwama S, Suga H, Banno R, Grinevich V, Arima H.: Knockdown of endoplasmic reticulum chaperone BiP leads to the death of parvocellular AVP/CRH neurons in mice. J Neuroendocrinol. 2023 Jan;35(1):e13223. doi: 10.1111/jne.13223.
  3. Kurimoto J, Takagi H, Miyata T, Kawaguchi Y, Hodai Y, Tsumura T, Hagiwara D, Kobayashi T, Yasuda Y, Sugiyama M, Onoue T, Iwama S, Suga H, Banno R, Katsuki T, Ando F, Uchida S, Arima H: Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency. Endocr J. 2023 Mar 28;70(3):295-304. doi: 10.1507/endocrj.EJ22-0339.
  4. Hayase A, Onoue T, Kobayashi T, Wada E, Handa T, Kinoshita T, Yamagami A, Yasuda Y, Iwama S, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Kuwatsuka Y, Ando M, Goto M, Arima H: Improved glycemic control after the use of flash glucose monitoring accompanied by improved treatment satisfaction in patients with non-insulin-treated type 2 diabetes: A post-hoc analysis of a randomized controlled trial. Prim Care Diabetes. 2023 Dec;17(6):575-580. doi: 10.1016/j.pcd.2023.09.009.
  5. Handa T, Onoue T, Kobayashi T, Wada E, Hayase A, Kinoshita T, Yamagami A, Yasuda Y, Iwama S, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Goto M, Arima H: Resting energy expenditure depends on energy intake during weight loss in people with obesity: a retrospective cohort study. Arch Endocrinol Metab. 2023 Mar 10;67(2):233-241. doi: 10.20945/2359-3997000000532.
2022
  1. Ito Y, Sun R, Yagimuma H, Taki K, Mizoguchi A, Kobayashi T, Sugiyama M, Onoue T, Tsunekawa T, Takagi H, Hagiwara D, Iwama S, Suga H, Konishi H, Kiyama H, Arima H, Banno R: Protein Tyrosine Phosphatase 1B Deficiency Improves Glucose Homeostasis in Type 1 Diabetes Treated With Leptin. Diabetes. 2022 Sep 1;71(9):1902-1914. doi: 10.2337/db21-0953.
  2. Kawaguchi Y, Hagiwara D, Tsumura T, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Yasuda Y, Iwama S, Suga H, Banno R, Grinevich V, Arima H: Knockdown of endoplasmic reticulum chaperone BiP leads to the death of parvocellular AVP/CRH neurons in mice. J Neuroendocrinol. 2023 Jan;35(1):e13223. doi: 10.1111/jne.13223.
  3. Kurimoto J, Takagi H, Miyata T, Kawaguchi Y, Hodai Y, Tsumura T, Hagiwara D, Kobayashi T, Yasuda Y, Sugiyama M, Onoue T, Iwama S, Suga H, Banno R, Katsuki T, Ando F, Uchida S, Arima H: Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency. Endocr J. 2023 Mar 28;70(3):295-304. doi: 10.1507/endocrj.EJ22-0339.
  4. Wada E, Onoue T, Kinoshita T, Hayase A, Handa T, Ito M, Furukawa M, Okuji T, Kobayashi T, Iwama S, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Goto M, Arima H: Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults. Reply to Sugiyama K and Saisho Y [letter]. Diabetologia. 2022 Jan;65(1):252-253. doi: 10.1007/s00125-021-05610-4.
  5. Ozaki H, Suga H, Sakakibara M, Soen M, Miyake N, Miwata T, Taga S, Nagai T, Kano M, Mitsumoto K, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Iwama S, Banno R, Iguchi G, Takahashi Y, Muguruma K, Inoue H, Arima H: Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state. Sci Rep. 2022 Oct 17;12(1):17381. doi: 10.1038/s41598-022-22405-8.
  6. Handa T, Onoue T, Kobayashi T, Wada E, Hayase A, Kinoshita T, Yamagami A, Yasuda Y, Iwama S, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Goto M, Arima H: Resting energy expenditure depends on energy intake during weight loss in people with obesity: a retrospective cohort study. Arch Endocrinol Metab. 2023 Mar 10;67(2):233-241. doi: 10.20945/2359-3997000000532.
  7. Hioki M, Kanehira N, Koike T, Saito A, Shimaoka K, Sakakibara H, Oshida Y, Akima H: Relationship between adiponectin and intramuscular fat content determined by ultrasonography in older adults. PLoS One. 2022 Jan 4;17(1):e0262271. doi: 10.1371/journal.pone.0262271. PMID: 34982778; PMCID: PMC8726469.
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  9. Yoshiko A, Maeda H, Takahashi H, Koike T, Tanaka N, Akima H: Contribution of skeletal muscle and serum lipids to muscle contraction induced by neuromuscular electrical stimulation in older individuals. Physiol Rep. 2022 Mar;10(6):e15236. doi: 10.14814/phy2.15236. PMID: 35312173; PMCID: PMC8935638.
  10. Tsuzuki T, Suzuki R, Kajun R, Yamada T, Iida T, Liu B, Koike T, Toyoda Y, Negishi T, Yukawa K: Combined effects of exercise training and D-allulose intake on endurance capacity in mice. Physiol Rep. 2022 May;10(9):e15297. doi: 10.14814/phy2.15297. PMID: 35546434; PMCID: PMC9095992.
  11. Yoshiko A, Maeda H, Takahashi H, Koike T, Tanaka N, Akima H: Importance of skeletal muscle lipid levels for muscle function and physical function in older individuals. Appl Physiol Nutr Metab. 2022 Jun 1;47(6):649-658. doi: 10.1139/apnm-2021-0685. Epub 2022 Jul 15. PMID: 35839289.
  12. Kitagawa F, Ogawa M, Yoshiko A, Oshida Y, Koike T, Akima H, Tanaka NI: Factors related to trunk intramuscular adipose tissue content - A comparison of younger and older men. Exp Gerontol. 2022 Oct 15;168:111922. doi: 10.1016/j.exger.2022.111922. PMID: 35964898.
2021
  1. Ryuge A, Kosugi T, Maeda K, Banno R, Gou Y, Zaitsu K, Ito T, Sato Y, Hirayama A, Tsubota S, Honda T, Nakajima K, Ozaki T, Kondoh K, Takahashi K, Kato N, Ishimoto T, Soga T, Nakagawa T, Koike T, Arima H, Yuzawa Y, Minokoshi Y, Maruyama S, Kadomatsu K: Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis. JCI Insight. 2021 Oct 22;6(20):e142464. doi: 10.1172/jci.insight.142464.
  2. Wada E, Onoue T, Kinoshita T, Hayase A, Handa T, Ito M, Furukawa M, Okuji T, Kobayashi T, Iwama S, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Goto M, Arima H: Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults. Reply to Sugiyama K and Saisho Y [letter]. Diabetologia. 2022 Jan;65(1):252-253. doi: 10.1007/s00125-021-05610-4.
  3. Taki K, Takagi H, Hirose T, Sun R, Yaginuma H, Mizoguchi A, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Hagiwara D, Ito Y, Iwama S, Suga H, Banno R, Sakano D, Kume S, Arima H: Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet. PLoS One. 2021 Mar 17;16(3):e0248065. doi: 10.1371/journal.pone.0248065.
  4. Sun R, Tsunekawa T, Hirose T, Yaginuma H, Taki K, Mizoguchi A, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Banno R, Bettler B, Arima H: GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice. Sci Rep. 2021 Sep 29;11(1):19296. doi: 10.1038/s41598-021-98590-9.
  5. Yaginuma H, Banno R, Sun R, Taki K, Mizoguchi A, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Arima H: Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice. J Pharmacol Sci. 2021 Dec;147(4):340-347. doi: 10.1016/j.jphs.2021.08.010.
  6. Mizoguchi A, Banno R, Sun R, Yaginuma H, Taki K, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Nagai T, Yamada K, Arima H: Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice. Sci Rep. 2021 Jun 18;11(1):12873. doi: 10.1038/s41598-021-92386-7.
  7. Kobayashi T, Iwama S, Sugiyama D, Yasuda Y, Okuji T, Ito M, Ito S, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Nishikawa H, Arima H: Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors. J Immunother Cancer. 2021 May;9(5):e002493. doi: 10.1136/jitc-2021-002493.
  8. Siriguleng S, Koike T, Natsume Y, Jiang H, Mu L, Oshida Y: Eicosapentaenoic acid enhances skeletal muscle hypertrophy without altering the protein anabolic signaling pathway. Physiol Res 2021 70(1):55-65. doi: 10.33549/physiolres.934534.
  9. Hioki M, Kanehira N, Koike T, Saito A, Takahashi H, Shimaoka K, Sakakibara H, Oshida Y, Akima H: Effect of electromyostimulation on intramyocellular lipids of the vastus lateralis in older adults: a randomized controlled trial. BMC Musculoskelet Disord. 2021 22(1):569. doi: 10.1186/s12891-021-04456-6.
  10. Ogawa M, Tanaka N, Yoshiko A, Oshida Y, Koike T, Akima H: Relationship between physical activity time and intramuscular adipose tissue content of the thigh muscle groups of younger and older men. Sci Rep 2021 11(1):19804. doi: 10.1038/s41598-021-99126-x.
  11. Natsume Y, Yamada T, Iida T, Ozaki N, Gou Y, Oshida Y, Koike. T: Investigation of D-allulose effects on high-sucrose diet-induced insulin resistance via hyperinsulinemic-euglycemic clamps in rats. Heliyon 2021 7(9):e08013. doi: 10.1016/j.heliyon.2021.e08013.
  12. Akima H, Maeda H, Koike T, Ishida K: Effect of elbow joint angles on electromyographic activity versus force relationships of synergistic muscles of the triceps brachii. PLoS One 2021 16(6):e0252644. doi: 10.1371/journal.pone.0252644.
  13. Gou Y, Liu B, Cheng M, Yamada T, Iida T, Wang S, Banno R, Koike T:D-Allulose ameliorates skeletal muscle insulin resistance in high-fat diet-fed rats. Molecules. 2021 26(20):6310. doi: 10.3390/molecules26206310. PMID: 34684891; PMCID: PMC8539500.
2020
  1. Wada E, Onoue T, Kobayashi T, Handa T, Hayase A, Ito M, Furukawa M, Okuji T, Okada N, Iwama S, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Kuwatsuka Y, Ando M, Goto M, Arima H: Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2020 Jun;8(1):e001115. doi: 10.1136/bmjdrc-2019-001115.
  2. Kasai T, Suga H, Sakakibara M, Ozone C, Matsumoto R, Kano M, Mitsumoto K, Ogawa K, Kodani Y, Nagasaki H, Inoshita N, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Takagi H, Hagiwara D, Iwama S, Goto M, Banno R, Takahashi J, Arima H: Hypothalamic contribution to pituitary functions is recapitulated in vitro using 3D-cultured human iPS cells. Cell Rep. 2020 Jan 7;30(1):18-24.e5. doi:
  3. 10.1016/j.celrep.2019.12.009.
  4. Miyata T, Hagiwara D, Hodai Y, Miwata T, Kawaguchi Y, Kurimoto J, Ozaki H, Mitsumoto K, Takagi H, Suga H, Kobayashi T, Sugiyama M, Onoue T, Ito Y, Iwama S, Banno R, Matsumoto M, Kawakami N, Ohno N, Sakamoto H, Arima H: Degradation of mutant protein aggregates within the endoplasmic reticulum of vasopressin neurons. iScience. 2020 Oct 7;23(10):101648. doi: 10.1016/j.isci.2020.101648.
  5. Kawaguchi Y, Hagiwara D, Miyata T, Hodai Y, Kurimoto J, Takagi H, Suga H, Kobayashi T, Sugiyama M, Onoue T, Ito Y, Iwama S, Banno R, Grinevich V, Arima H: Endoplasmic reticulum chaperone BiP/GRP78 knockdown leads to autophagy and cell death of arginine vasopressin neurons in mice. Sci Rep. 2020 Nov 12;10(1):19730. doi: 10.1038/s41598-020-76839-z.
  6. Takagi H, Hagiwara D, Handa T, Sugiyama M, Onoue T, Tsunekawa T, Ito Y, Iwama S, Goto M, Suga H, Banno R, Takahashi K, Matsui S, Arima H: Diagnosis of central diabetes insipidus using a vasopressin radioimmunoassay during hypertonic saline infusion. Endocr J. 2020 Mar 28;67(3):267-274. doi: 10.1507/endocrj.EJ19-0224.
  7. Okada N, Iwama S, Okuji T, Kobayashi T, Yasuda Y, Wada E, Onoue T, Goto M, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Hase T, Morise M, Kanda M, Yokota K, Hashimoto N, Ando M, Fujimoto Y, Nagino M, Kodera Y, Fujishiro M, Hibi H, Sone M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H: Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Br J Cancer. 2020 Mar;122(6):771-777. doi: 10.1038/s41416-020-0736-7.
  8. Onoue T, Goto M, Wada E, Furukawa M, Okuji T, Okada N, Kobayashi T, Iwama S, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Seino Y, Suga H, Banno R, Hamada Y, Ando M, Yamamori E, Arima H: Dipeptidyl peptidase-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels in patients with type 2 diabetes: A randomized controlled trial. PLoS One. 2020 Jan 28;15(1):e0228004. doi: 10.1371/journal.pone.0228004.
  9. Kobayashi T, Iwama S, Yasuda Y, Okada N, Okuji T, Ito M, Onoue T, Goto M, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Suga H, Banno R, Yokota K, Hase T, Morise M, Hashimoto N, Ando M, Fujimoto Y, Hibi H, Sone M, Ando Y, Akiyama M, Hasegawa Y, Arima H: Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study. J Immunother Cancer. 2020 Jul;8(2):e000779. doi: 10.1136/jitc-2020-000779.
  10. Yoshiko A, Katayama K, Ishida K, Ando R, Koike T, Oshida Y, Akima H: Muscle deoxygenation and neuromuscular activation in synergistic muscles during intermittent exercise under hypoxic conditions. Sci Rep 2020 10(1):295. doi:10.1038/s41598-019-57099 -y.
  11. Ogawa M, Yoshiko A, Tanaka N, Koike T, Oshida Y, Akima H: Comparing intramuscular adipose tissue on T1-weighted and two-point Dixon images. PLoS ONE 2020 15(4): e0231156.https://doi.org/10.1371/journal. pone.0231156
  12. Hioki M, Kanehira N, Koike T, Saito A, Shimaoka K, Sakakibara H, Oshida Y, Akima H: Age-related changes in muscle volume and intramuscular fat content in quadriceps femoris and hamstrings. Exp Gerontol 2020 132:110834. https://doi.org/10.1016/j.exger.2020.110834
  13. Akima H, Maeda H, Koike T, Ishida K, Ando R: Comparison of fascicle behaviors between superficial and deeper muscles of triceps brachii during isometric contractions. J. Electromyogr. Kinesiol. 2020 54:https://doi.org/10.1016/j.jelekin.2020.102452

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