Introduction

Insulin resistance is a major pathological condition associated with lifestyle-related diseases such as obesity, diabetes and hypertension. Insulin resistance also can play a critical role in aging. Our laboratory aims to clarify the mechanism associated with insulin resistance and its countermeasure and to contribute to the prevention of lifestyle-related diseases. In particular, focusing on the prevention by exercise and nutritional interventions, we do human studies, in vivo animal studies, and molecular biological studies. Recently we also started research on glucose and energy metabolism in the central nervous system.

Research Projects

1. Basic and clinical studies on insulin resistance

In addition to the role of insulin resistance in glucose metabolism, we have been studying the role of insulin resistance in skeletal muscle and brain in recent years. Skeletal muscle, one of the main regulatory organs of glucose, has been gaining more attention as the impact of sarcopenia (age-related skeletal muscle loss), which is the main factor of physical weakness in the elderly. Healthy muscle is critical for QOL of the elderly. Age-related cognitive decline and increase of dementia are also serious concerns in an aging society. The prevention and treatment of sarcopenia and cognitive decline by exercise and nutrition therapy, which can optimize insulin resistance, are highly expected. With this background, using glucose metabolism, skeletal muscle quality and quantity, and chronic inflammation in the brain as indicators, we aim to find the way to decrease the risk of sarcopenia and cognitive decline or dementia.

2. Regulatory mechanisms of glucose metabolism and energy balance

Energy balance is regulated by central nervous system. While obesity, which is the cause of lifestyle-related diseases, is spreading all over the world at pandemic level, effective medical treatments have not yet been established. Therefore, elucidation of the mechanisms of obesity and the establishment of obesity treatment is expected. Our research focus is the mechanisms by which a high-fat diet impairs both glucose and energy metabolism, and the regulatory mechanisms of glucose metabolism by central nervous system as well. Especially, we are focused on protein tyrosine phosphatase 1B（PTP1B）that is the regulatory factor of insulin receptor signaling, leptin receptor signaling and inflammation. We use various genetically modified mice so that we can elucidate the regulatory mechanisms of glucose metabolism and energy balance.

Faculty Members

Faculty	Position	Department
KOIKE Teruhiko	Professor	Sports Medicine
Banno Ryoichi	Associate Professor	Sports Medicine

Bibliography

• 2019

  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

  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

  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

  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

• 2015

  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

  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

  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

  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

Research Keywords

exercise therapy、 physical training、 skeletal muscle、 glucose metabolism、 insulin resistance、 diabetes mellitus、 obesity

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First Steps to Graduate Admission

 If you have interests in our laboratory, please make contact with us !! To visit our laboratory and talk with us may provide you with more information. If you want to make contact with us, please send an e-mail to koike@htc.nagoya-u.ac.jp (KOIKE Teruhiko) in advance.