Faculty Profiles - ARIMA, Hiroshi

Papers - ARIMA, Hiroshi

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Wolfram症候群モデルマウスは脱水負荷によりバソプレシン分泌不全を呈する

栗本隼樹, 高木博史, 津村哲郎, 蓬臺優一, 川口頌平, 宮田崇, 萩原大輔, 須賀英隆, 田部勝也, 谷澤幸生, 有馬寛

日本内分泌学会雑誌 Vol. 97 ( 1 ) page： 261 - 261 2021.4

AVPニューロン特異的BiPノックダウンはAVPニューロンにおけるオートファジーと細胞死を誘導する

川口頌平, 萩原大輔, 津村哲郎, 蓬臺優一, 栗本隼樹, 宮田崇, 高木博史, 須賀英隆, Grinevich Valery, 有馬寛

日本内分泌学会雑誌 Vol. 97 ( 1 ) page： 261 - 261 2021.4

食塩過剰摂取は高脂肪食によって惹起される膵β細胞増殖を抑制して耐糖能を悪化させる

滝啓吾, 高木博史, 廣瀬友矩, 孫汝楠, 柳沼裕史, 杉山摩利子, 伊藤禎浩, 坂野僚一, 有馬寛

日本内分泌学会雑誌 Vol. 97 ( 1 ) page： 321 - 321 2021.4

Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet. Reviewed

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.

PLos One Vol. 16 ( 3 ) page： e0248065 2021.3

Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet. International journal Open Access

Keigo Taki, Hiroshi Takagi, Tomonori Hirose, Runan Sun, Hiroshi Yaginuma, Akira Mizoguchi, Tomoko Kobayashi, Mariko Sugiyama, Taku Tsunekawa, Takeshi Onoue, Daisuke Hagiwara, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Daisuke Sakano, Shoen Kume, Hiroshi Arima

PloS one Vol. 16 ( 3 ) page： e0248065 2021.3

Language：English Publishing type：Research paper (scientific journal)

Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.

DOI： 10.1371/journal.pone.0248065

Open Access

Web of Science

PubMed

Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine. International journal

Mayuko Kano, Hidetaka Suga, Hiroshi Arima

Journal of the Endocrine Society Vol. 5 ( 3 ) page： bvaa188 2021.3

Language：English Publishing type：Research paper (scientific journal)

The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a 3-dimensional (3D) culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in 3D cultures of mouse ESCs. The ESCs were found to differentiate into both nonneural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the 2 tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from nonneural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

DOI： 10.1210/jendso/bvaa188

Web of Science

PubMed

High-fat Feeding Causes Inflammation and Insulin Resistance in the Ventral Tegmental Area in Mice. Reviewed

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, Arima H.

Neuroscience Vol. 18 ( 461 ) page： 72 - 79 2021.2

Hypothalamic-pituitary organoid generation through the recapitulation of organogenesis. Reviewed

Hajime Ozaki, Hidetaka Suga, Hiroshi Arima

Development, growth & differentiation Vol. 63 ( 2 ) page： 154 - 165 2021.2

Language：English Publishing type：Research paper (scientific journal)

This paper overviews the development and differentiation of the hypothalamus and pituitary gland from embryonic stem (ES) and induced pluripotent stem (iPS) cells. It is important to replicate the developmental process in vivo to create specific cells/organoids from ES/iPS cells. We also introduce the latest findings and discuss future issues for clinical application. Neuroectodermal progenitors are induced from pluripotent stem cells by strictly removing exogenous patterning factors during the early differentiation period. The induced progenitors differentiate into rostral hypothalamic neurons, in particular magnocellular vasopressin+ neurons. In three-dimensional cultures, the ES/iPS cells differentiate into hypothalamic neuroectoderm as well as non-neural head ectoderm back to back. Rathke's pouch-like structures self-organize at the interface between the two layers and generated various endocrine cells, including corticotrophs and somatotrophs from the Rathke's pouch-like structures. Our next objective is to sophisticate our stepwise methodology to establish the novel transplantation treatment for hypopituitarism and to apply it to developmental disease models.

DOI： 10.1111/dgd.12719

Web of Science

PubMed

胆管癌に伴う閉塞性黄疸の解除後、約3ヵ月でインスリン離脱となった1例

木下珠希, 杉山摩利子, 有馬寛

糖尿病 Vol. 64 ( 2 ) page： 151 - 151 2021.2

Open-label, multicenter, dose-titration study to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone. Reviewed

Arima H, Goto K, Motozawa T, Mouri M, Watanabe R, Hirano T, Ishikawa SE

Endocrine journal Vol. 68 ( 1 ) page： 17 - 29 2021.1

イピリムマブとニボルマブの併用療法後に原発性副腎皮質機能低下症と潜在性甲状腺機能低下症を認めた一例 Reviewed

山田紗矢加, 岩間信太郎, 小林朋子, 伊藤雅晃, 奥地剛之, 安田康紀, 有馬寛

日本内分泌学会雑誌 Vol. 96 ( 3 ) page： 720 - 720 2021.1

Efficacies of programmed cell death 1 ligand 1 blockade in non-small cell lung cancer patients with acquired resistance to prior programmed cell death 1 inhibitor and development of diabetic ketoacidosis caused by two different etiologies: a retrospective case series Reviewed

Ishi Azusa, Tanaka Ichidai, Iwama Shintaro, Sakakibara Toshihiro, Mastui Toshinori, Kobayashi Tomoko, Hase Tetsunari, Morise Masahiro, Sato Mitsuo, Arima Hiroshi, Hashimoto Naozumi

ENDOCRINE JOURNAL Vol. 68 ( 5 ) page： 613 - 620 2021

Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice Reviewed

Hiroshi Yaginuma, Ryoichi Banno, Runan Sun, Keigo Taki, Akira Mizoguchi, Tomoko Kobayashi, Mariko Sugiyama, Taku Tsunekawa, Takeshi Onoue, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Hiroshi Arima

JOURNAL OF PHARMACOLOGICAL SCIENCES Vol. 147 ( 4 ) page： 340 - 347 2021

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

We investigated whether peripheral combination treatment of a sodium-glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptozotocin to produce IDDM. IDDM mice were then divided into five groups: SGLT2 inhibitor treatment alone, leptin treatment alone, leptin and SGLT2 inhibitor co-treatment, untreated IDDM mice, and healthy mice groups. The blood glucose (BG) level at the end of the dark cycle was measured, and a glucose tolerance test (GTT) was performed and compared between the five groups. Leptin was peripherally administered at 20 mu g/day using an osmotic pump, and an SGLT2 inhibitor, ipragliflozin, was orally administered at 3 mg/kg/day. Monotherapy with SGLT2 inhibitor or leptin significantly improved glucose metabolism in mice as evaluated by BG and GTT compared with the untreated group, whereas the co-treatment group with SGLT2 inhibitor and leptin further improved glucose metabolism as compared with the monotherapy group. Notably, glucose metabolism in the co-treatment group improved to the same level as that in the healthy mice group. Thus, peripheral combination treatment with leptin and SGLT2 inhibitor improved glucose metabolism in IDDM mice without the use of insulin. (C) 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

DOI： 10.1016/j.jphs.2021.08.010

Web of Science

PubMed

Preoperative and long-term efficacy and safety of lanreotide autogel in patients with thyrotropin-secreting pituitary adenoma: a multicenter, single-arm, phase 3 in Japan Reviewed

Shimatsu Akira, Nakamura Akinobu, Takahashi Yutaka, Fujio Shingo, Satoh Fumitoshi, Tahara Shigeyuki, Nishioka Hiroshi, Takano Koji, Yamashita Miho, Arima Hiroshi, Tominaga Atsushi, Tateishi Shohei, Matsushita Yusaku

ENDOCRINE JOURNAL Vol. 68 ( 7 ) page： 791 - 805 2021

Arima Hiroshi, Goto Koichi, Motozawa Tomohisa, Mouri Makoto, Watanabe Ryo, Hirano Takahiro, Ishikawa San-e

ENDOCRINE JOURNAL Vol. 68 ( 1 ) page： 17 - 29 2021

Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine Invited Reviewed

Kano M, Suga H, Arima H.

J Endocr Soc Vol. 5 ( 3 ) page： bvaa188 2020.12

Anti-pituitary antibodies as a marker of autoimmunity in pituitary glands.

Iwama S, Arima H

Endocrine journal Vol. 67 ( 11 ) page： 1077 - 1083 2020.11

Endoplasmic reticulum chaperone BiP/GRP78 knockdown leads to autophagy and cell death of arginine vasopressin neurons in mice. Reviewed

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

Scientific reports Vol. 10 ( 1 ) page： 19730 2020.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title>The immunoglobulin heavy chain binding protein (BiP), also referred to as 78-kDa glucose-regulated protein (GRP78), is a pivotal endoplasmic reticulum (ER) chaperone which modulates the unfolded protein response under ER stress. Our previous studies showed that BiP is expressed in arginine vasopressin (AVP) neurons under non-stress conditions and that BiP expression is upregulated in proportion to the increased AVP expression under dehydration. To clarify the role of BiP in AVP neurons, we used a viral approach in combination with shRNA interference for BiP knockdown in mouse AVP neurons. Injection of a recombinant adeno-associated virus equipped with a mouse AVP promoter and BiP shRNA cassette provided specific BiP knockdown in AVP neurons of the supraoptic (SON) and paraventricular nuclei (PVN) in mice. AVP neuron-specific BiP knockdown led to ER stress and AVP neuronal loss in the SON and PVN, resulting in increased urine volume due to lack of AVP secretion. Immunoelectron microscopy of AVP neurons revealed that autophagy was activated through the process of AVP neuronal loss, whereas no obvious features characteristic of apoptosis were observed. Pharmacological inhibition of autophagy by chloroquine exacerbated the AVP neuronal loss due to BiP knockdown, indicating a protective role of autophagy in AVP neurons under ER stress. In summary, our results demonstrate that BiP is essential for the AVP neuron system.

DOI： 10.1038/s41598-020-76839-z

Web of Science

PubMed

Other Link： http://www.nature.com/articles/s41598-020-76839-z

Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons. Reviewed International journal

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

iScience Vol. 23 ( 10 ) page： 101648 - 101648 2020.10

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER.

DOI： 10.1016/j.isci.2020.101648

Web of Science

PubMed

Generation of four induced pluripotent stem cell lines (FHUi003-A, FHUi003-B, FHUi004-A and FHUi004-B) from two affected individuals of a familial neurohypophyseal diabetes insipidus family Invited

Yoshida Satoru, Okura Hanayuki, Suga Hidetaka, Soen Mika, Kawaguchi Yohei, Kurimoto Junki, Miyata Takashi, Takagi Hiroshi, Arima Hiroshi, Fujikawa Tatsuya, Otsuka Fumio, Matsuyama Akifumi

STEM CELL RESEARCH Vol. 48 page： 101960 - 101960 2020.10

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Papers - ARIMA, Hiroshi