Faculty Profiles - ARIMA, Hiroshi

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

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 Open Access

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 Open Access

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

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

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 Open Access

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

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 Open Access

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

The Smart Life Stay (SLS) program: effects of a lifestyle intervention program in combination with health tourism and health guidance for type 2 diabetes (vol 10, 33, 2020) Open Access

Matsushita, M; Muramoto, A; Nomura, E; Eguchi, Y; Kato, A; Sano, Y; Kabayama, M; Arakawa, M; Oguma, Y; Yabe, D; Matsunaga, M; Yatsuya, H; Arima, H; Tsushita, K

NUTRITION & DIABETES Vol. 10 ( 1 ) page： 34 2020.9

Higher level of body mass index (≥ 22 kg/m<SUP>2</SUP>) is a useful predictor of non-insulin requirement in Slowly Progressive Insulin-Dependent (Type 1) Diabetes Mellitus (SPIDDM) Reviewed

Onoue, T; Wada, E; Hayase, A; Handa, T; Furukawa, M; Kobayashi, T; Goto, M; Arima, H

DIABETOLOGIA Vol. 63 ( SUPPL 1 ) page： S176 - S176 2020.9

The regulation of glucose metabolism by astrocytes in diet induced obesity mice Reviewed

Sugiyama, M; Banno, R; Sun, R; Yaginuma, H; Taki, K; Takagi, H; Ito, Y; Yamanaka, K; Arima, H

DIABETOLOGIA Vol. 63 ( SUPPL 1 ) page： S266 - S266 2020.9

Protein tyrosine phosphatase 1B deficiency enhances leptin action to improve glucose homeostasis in IDDM treatment with leptin

Ito, Y; Banno, R; Sun, R; Yaginuma, H; Taki, K; Sugiyama, M; Tsunekawa, T; Takagi, H; Arima, H

DIABETOLOGIA Vol. 63 ( SUPPL 1 ) page： S12 - S12 2020.9

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

Yaginuma, H; Banno, R; Sun, R; Taki, K; Sugiyama, M; Tsunekawa, T; Takagi, H; Ito, Y; Arima, H

DIABETOLOGIA Vol. 63 ( SUPPL 1 ) page： S259 - S260 2020.9

【糖尿病・内分泌代謝疾患における妊娠と出産】中枢性尿崩症

高木博史, 有馬寛

糖尿病・内分泌代謝科 Vol. 51 ( 3 ) page： 211 - 214 2020.9

The Smart Life Stay (SLS) program: effects of a lifestyle intervention program in combination with health tourism and health guidance for type 2 diabetes International journal Open Access

Matsushita Madoka, Muramoto Akiko, Nomura Eri, Eguchi Yukari, Kato Ayako, Sano Yoshiko, Kabayama Mai, Arakawa Masashi, Oguma Yuko, Yabe Daisuke, Matsunaga Masaaki, Yatsuya Hiroshi, Arima Hiroshi, Tsushita Kazuyo

NUTRITION & DIABETES Vol. 10 ( 1 ) page： 33 - 33 2020.8

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

BACKGROUND: The aim of this study was to determine the effectiveness of the Smart Life Stay (SLS) program, which is an experience-oriented stayover program, in combination with health tourism and mandatory health guidance on glucose metabolism after 2 years. METHODS: The participants of the SLS program (n = 792) were recruited from a database of 23 medical insurers. They underwent a mandatory health examination termed Specific Health Checkups in 2014. The participants were included if they had diabetes or were at a high risk of diabetes and if they satisfied the following inclusion criteria: (1) body mass index (BMI; kg/m2) > 25, or (2) waist circumference (WC; cm) > 85 for men and > 90 for women, or (3) hemoglobin A1c (HbA1c; %) > 5.6, or (4) fasting plasma glucose (FPG; mg/dl) > 100. Individuals who corresponded to one or more items were included as study participants. The control subjects (n = 3645) were nonparticipants of the program who were selected from the database and met the inclusion criteria. The lifestyle changes and changes in mean BMI, WC, FPG, and HbA1c in both groups from baseline to 2-year follow-up were compared by inverse probability weighting of a propensity score. RESULTS: The percentage of people who exercised regularly increased significantly in the SLS group compared with the control group. In the SLS group, BW, BMI, and WC significantly decreased by 1.75 kg, 0.60 kg/m2, and 1.45 cm, respectively, whereas in the control group, WC, FPG, and HbA1c increased significantly by 0.38 cm, 3.37 mg/dl, and 0.12%, respectively. The comparison between groups revealed that the BW, BMI, WC, FPG, and HbA1c improved significantly in the SLS group. CONCLUSIONS: The SLS program is suggested to help improve glucose metabolism. This program could be a feasible option as a lifestyle intervention program for diabetes.

DOI： 10.1038/s41387-020-00136-x