研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice. 査読有り国際誌 Open Access

Iwakura H, Hosoda K, Son C, Fujikura J, Tomita T, Noguchi M, Ariyasu H, Takaya K, Masuzaki H, Ogawa Y, Hayashi T, Inoue G, Akamizu T, Hosoda H, Kojima M, Itoh H, Toyokuni S, Kangawa K, Nakao K

The Journal of biological chemistry 280 巻 ( 15 ) 頁： 15247 - 56 2005年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

We developed and analyzed two types of transgenic mice: rat insulin II promoter-ghrelin transgenic (RIP-G Tg) and rat glucagon promoter-ghrelin transgenic mice (RGP-G Tg). The pancreatic tissue ghrelin concentration measured by C-terminal radioimmunoassay (RIA) and plasma desacyl ghrelin concentration of RIP-G Tg were about 1000 and 3.4 times higher than those of nontransgenic littermates, respectively. The pancreatic tissue n-octanoylated ghrelin concentration measured by N-terminal RIA and plasma n-octanoylated ghrelin concentration of RIP-G Tg were not distinguishable from those of nontransgenic littermates. RIP-G Tg showed suppression of glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion, pancreatic insulin mRNA and peptide levels, β cell mass, islet architecture, and GLUT2 and PDX-1 immunoreactivity in RIP-G Tg pancreas were not significantly different from those of nontransgenic littermates. Islet batch incubation study did not show suppression of insulin secretion of RIP-G Tg in vitro. The insulin tolerance test showed lower tendency of blood glucose levels in RIP-G Tg. Taking lower tendency of triglyceride level of RIP-G Tg into consideration, these results may indicate that the suppression of insulin secretion is likely due to the effect of desacyl ghrelin on insulin sensitivity. RGP-G Tg, in which the pancreatic tissue ghrelin concentration measured by C-RIA was about 50 times higher than that of nontransgenic littermates, showed no significant changes in insulin secretion, glucose metabolism, islet mass, and islet architecture. The present study raises the possibility that desacyl ghrelin may have influence on glucose metabolism. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M411358200

その他リンク： http://orcid.org/0000-0001-8033-0736

CYP3A induction more impairs endotoxemic liver injury via reactive oxygen species in rats

Minamiyama, Y; Takemura, S; Kodai, S; Toyokuni, S; Yoshikawa, T; Okada, S

GASTROENTEROLOGY 128 巻 ( 4 ) 頁： A709 - A709 2005年4月

Long-term culture of mouse male germline stem cells under serum-or feeder-free conditions. 査読有り国際誌

Kanatsu-Shinohara M, Miki H, Inoue K, Ogonuki N, Toyokuni S, Ogura A, Shinohara T

Biology of reproduction 72 巻 ( 4 ) 頁： 985 - 91 2005年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biology of Reproduction

Spermatogonial stem cells are the only stem cells in the body that transmit genetic information to the next generation. These cells can be cultured for extended periods in the presence of serum and feeder cells. However, little is known about factors that regulate self-renewal division of spermatogonial stem cells. In this investigation we examined the possibility of establishing culture systems for spermatogonial stem cells that lack serum or a feeder cell layer. Spermatogonial stem cells could expand in serum-free conditions on mouse embryonic fibroblasts (MEFs), or were successfully cultivated without feeder cells on a laminin-coated plate. However, they could not expand when both serum and feeder cells were absent. Although the cells cultured on laminin differed phenotypically from those on feeder cells, they grew exponentially for at least 6 mo, and produced normal, fertile progeny following transplantation into infertile mouse testis. This culture system will provide a new opportunity for understanding the regulatory mechanism that governs spermatogonial stem cells. © 2005 by the Society for the Study of Reproduction, Inc.

DOI： 10.1095/biolreprod.104.036400

CYP3A induction more impairs endotoxemic liver injury via reactive oxygen species in rats 国際誌

Minamiyama, Y, Takemura, S, Kodai, S, Toyokuni, S, Yoshikawa, T, Okada, S

GASTROENTEROLOGY 128 巻 ( 4 ) 頁： A709 - A709 2005年4月

多発隆起型早期胆嚢癌の1切除例

浦井俊二, 早雲孝信, 羽生泰樹, 河村卓二, 塩せいじ, 池浦司, 吉野琢哉, 平井潔, 豊國伸哉

日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 102 巻 ( 3 ) 頁： 340 - 345 2005年3月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般財団法人日本消化器病学会

症例は75歳，女性．スクリーニングの腹部超音波検査で胆嚢内に複数の隆起性病変を認め，入院となった．CT，ERCPなどの所見より隆起型胆嚢癌と診断し，開腹胆摘術を行った．病理組織学的に3個の乳頭腺癌を認め，深達度は最大の腫瘍がmp，他はmであった．全割切片による検索で上皮内癌を認め，癌周囲には異形成をともなっていた．Ki-67標識率は固有上皮部2.6％，異形成部9.7％，上皮内癌部26.6％，癌部36.9％であった．p53蛋白過剰発現を認めなかった．<br>

DOI： 10.11405/nisshoshi.102.340

CiNii Research

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Selenium Supplementation Rescues Cardiac Output in Patients with Severe Heart Failure who are Intractable to ACE Inhibitors and β-Blockers(Heart Failure, Clinical 14 (M), The 69th Annual Scientific Meeting of the Japanese Circulation Society)

Hiraoka Yuuji, Kihara Yasuki, Sarazawa Katsuhiko, Inai Yoshihito, Kitagawa Motoaki, Takahashi Nobuki, Hamanaka Ichirou, Yamazaki Taketoshi, Akagi Tadasu, Hama Norio, Tanabe Masato, Sakurai Hiromu, Toyokuni Shinya, Ueda Kinzou

Circulation journal : official journal of the Japanese Circulation Society 69 巻 ( 0 ) 頁： 310 2005年3月

Circulation journal : official journal of the Japanese Circulation Society 69 巻 ( 0 ) 2005年3月

Genetic selection of mouse male germline stem cells in vitro: offspring from single stem cells. 査読有り国際誌 Open Access

Kanatsu-Shinohara M, Toyokuni S, Shinohara T

Biology of reproduction 72 巻 ( 1 ) 頁： 236 - 40 2005年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biology of Reproduction

Spermatogenesis originates from a small population of spermatogonial stem cells. These cells are believed to divide infinitely and support spermatogenesis throughout life in the male. In this investigation, we examined the possibility of deriving transgenic offspring from single spermatogonial stem cells. Spermatogonial stem cells were transfected in vitro with a plasmid vector containing a drug resistant gene. Stably transfected stem cell clones were isolated by in vitro drug selection; these clones were expanded and used to produce transgenic progeny following spermatogonial transplantation into infertile recipients. An average of 49% of the offspring carried the transgene, and the recipient mice continued to produce monoclonal transgenic progeny a year after transplantation. Thus, a somatic cell-based genetic approach can be used to modify and select clones of spermatogonial stem cells in a manner similar to embryonic stem cells. The feasibility of genetic selection using postnatal spermatogonial stem cells demonstrates their extensive proliferative potential and provides the opportunity to develop new methods for generating stable animal transgenics or for germline gene therapy.

DOI： 10.1095/biolreprod.104.035659

Spermatogenesis from epiblast and primordial germ cells following transplantation into postnatal mouse testis. 査読有り国際誌 Open Access

Chuma S, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S, Hosokawa M, Nakatsuji N, Ogura A, Shinohara T

Development (Cambridge, England) 132 巻 ( 1 ) 頁： 117 - 22 2005年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Development

Primordial germ cells (PGCs) are derived from a population of pluripotent epiblast cells in mice. However, little is known about when and how PGCs acquire the capacity to differentiate into functional germ cells, while keeping the potential to derive pluripotent embryonic germ cells and teratocarcinomas. In this investigation, we show that epiblast cells and PGCs can establish colonies of spermatogenesis after transfer into postnatal seminiferous tubules of surrogate infertile mice. Furthermore, we obtained normal fertile offspring by microinsemination using spermatozoa or spermatids derived from PGCs harvested from fetuses as early as 8.5 days post coitum. Thus, fetal male germ cell development is remarkably flexible, and the maturation process, from epiblast cells through PGCs to postnatal spermatogonia, can occur in the postnatal testicular environment. Primordial germ cell transplantation techniques will also provide a novel tool to assess the developmental potential of PGCs, such as those manipulated in vitro or recovered from embryos harboring lethal mutations.

DOI： 10.1242/dev.01555

Reduction of dibetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice. 査読有り

Naito Y, Akagiri S, Uchiyama K, Kokura S, Yoshida N, Hasegawa G, Nakamura N, Ichikawa H, Toyokuni S, Ijichi T, Yoshikawa T.

Biofactors 23 巻頁： 85-98 2005年

Genetic and epigenetic properties of mouse male germline stem cells during long-term culture. 査読有り

Kanatsu-Shinohara M, Ogonuki N, Iwano T, Lee J, Kazuki Y, Inoue K, Miki H, Takehashi M, Toyokuni S, Shinkai Y, Oshimura M, Ishino F, Ogura A, Shinohara T.

Developmnet 132 巻頁： 4155-4163 2005年

Establishment of a diabetic mouse model with progressive diabetic nephropathy. 査読有り

Inada A, Nagai K, Arai H, Miyazaki J, Nomura K, Kanamori H, Toyokuni S, Yamada Y, Bonner-Weir S, Weir GC, Fukatsu A, Seino Y.

Am. J. Pathol. 167 巻頁： 327-336 2005年

Free radical-induced carcinogenesis: Target genes and fragile genome sites

Toyokuni, S; Akatsuka, S; Aung, TT; Dutta, KK

FREE RADICAL RESEARCH 39 巻頁： S30 - S30 2005年

Imidapril, an angiotensin-converting enzyme inhibitor, reduces diabetes-induced renal oxidative damage in mice

Naito Y, Uchiyama K, Akagiri S, Aoi W, Hasegawa G, Nakamura N, Kokura S, Yoshida N, Ichikawa H, Toyokuni S, Yoshikawa T

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 37 巻 ( 1 ) 頁： 29 - 37 2005年

Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice

Naito Y, Akagiri S, Uchiyama K, Kokura S, Yoshida N, Hasegawa G, Nakamura N, Ichikawa H, Toyokuni S, Ijichi T, Yoshikawa T

BIOFACTORS 23 巻 ( 2 ) 頁： 85 - 95 2005年

Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice.

Naito Y, Akagiri S, Uchiyama K, Kokura S, Yoshida N, Hasegawa G, Nakamura N, Ichikawa H, Toyokuni S, Ijichi T, Yoshikawa T

BioFactors (Oxford, England) 23 巻 ( 2 ) 頁： 85 - 95 2005年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BioFactors

Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Oxykine is the cantaloupe melon extract rich in vegetal superoxide dismutase covered by polymeric films of wheat matrix gliadin. In this study, we examined whether chronic oral administration of oxykine could prevent the progression of diabetic nephropathy induced by oxidative stress using preclinical rodent model of type 2 diabetes. We used female db/db mice and their non-diabetic db/m littermates. The mice were divided into the following three groups: non-diabetic db/m; diabetic db/db, and diabetic db/db treated with oxykine. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were preformed on 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the oxykine-treated group and the non-treated db/db group, however both groups kept significantly high levels rather than db/m mice. The relative mesangial area calculated by mesangial area/total glomerular area ratio was significantly ameliorated in the oxykine treated group compared with non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with oxykine. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than that of oxykine-treated db/db mice. In this study, treatment of oxykine ameliorated the progression and acceleration of diabetic nephropathy for rodent model of type 2 diabetes. These results indicated that the oxykine reduced the diabetes-induced oxidative stress and renal mesangial cell injury. In conclusion, oxykine might be a novel approach for the prevention of diabetes nephropathy. © 2005 - IOS Press and the authors. All rights reserved.

DOI： 10.1002/biof.5520230204

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PubMed

Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice 査読有り

Y Naito, S Akagiri, K Uchiyama, S Kokura, N Yoshida, G Hasegawa, N Nakamura, H Ichikawa, S Toyokuni, T Ijichi, T Yoshikawa

BIOFACTORS 23 巻 ( 2 ) 頁： 85 - 95 2005年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IOS PRESS

Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Oxykine is the cantaloupe melon extract rich in vegetal superoxide dismutase covered by polymeric films of wheat matrix gliadin. In this study, we examined whether chronic oral administration of oxykine could prevent the progression of diabetic nephropathy induced by oxidative stress using preclinical rodent model of type 2 diabetes. We used female db/db mice and their non-diabetic db/m littermates. The mice were divided into the following three groups: non-diabetic db/m; diabetic db/db, and diabetic db/db treated with oxykine. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were preformed on 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the oxykine-treated group and the non-treated db/db group, however both groups kept significantly high levels rather than db/m mice. The relative mesangial area calculated by mesangial area/total glomerular area ratio was significantly ameliorated in the oxykine treated group compared with non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with oxykine. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than that of oxykine-treated db /db mice. In this study, treatment of oxykine ameliorated the progression and acceleration of diabetic nephropathy for rodent model of type 2 diabetes. These results indicated that the oxykine reduced the diabetes-induced oxidative stress and renal mesangial cell injury. In conclusion, oxykine might be a novel approach for the prevention of diabetes nephropathy.

Web of Science

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Imidapril, an angiotensin-converting enzyme inhibitor, reduces diabetes-induced renal oxidative damage in mice 査読有り

Y Naito, K Uchiyama, S Akagiri, W Aoi, G Hasegawa, N Nakamura, S Kokura, N Yoshida, H Ichikawa, S Toyokuni, T Yoshikawa

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 37 巻 ( 1 ) 頁： 29 - 37 2005年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

The aim of the present study was to determine whether imidapril, an angiotensin-converting enzyme inhibitor, prevents diabetic nephropathy and to determine the effect of imidapril on oxidative damage in the diabetic glomeruli in mice. We used female BKS.cg-m+Lepr(db)/+Lepr(db) (db/db) mice, a rodent model of type 2 diabetes, and their non-diabetic db/m littermates. The mice were divided into the following four groups: non-diabetic db/m, diabetic db/db, and diabetic db/db treated with imidapril at doses of 1 mg/kg and 5 mg/kg. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were performed for 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the imidapril-treated group and the non-treated db/db group. The systolic blood pressure was significantly increased in db/db mice compared with db/m mice. The increased blood pressure was significantly reduced by the treatment with imidapril at a dose of 5 mg/kg. The relative mesangial area calculated by the mesangial area/total glomerular area ratio was significantly ameliorated in the imidapril-treated group compared with the non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with imidapril in a dose-dependent manner. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than in the imidapril-treated db/db mice. In conclusion, imidapril prevented the progression of diabetic nephropathy in mice, not only by decreasing the glomerular pressure but also by decreasing the oxidative stress in glomerular cells.

Web of Science

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Control of the peri-operative oxidative stress enables fast recovery from myocardial ischemic damage in cardic surgery. 査読有り

Takaba K, Matsumura K, Miwa S, Yamazaki K, Nishina K, Nomoto T, Toyokuni S, Hyon SH, Ikeda T, Komeda M

International Redox Network 2005（2005.11.9－11. kyoto） 2005年

Generation of pluripotent stem cells from neonatal mouse testis. 査読有り国際誌

Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T

Cell 119 巻 ( 7 ) 頁： 1001 - 12 2004年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cell

Although germline cells can form multipotential embryonic stem (ES)/embryonic germ (EG) cells, these cells can be derived only from embryonic tissues, and such multipotent cells have not been available from neonatal gonads. Here we report the successful establishment of ES-like cells from neonatal mouse testis. These ES-like cells were phenotypically similar to ES/EG cells except in their genomic imprinting pattern. They differentiated into various types of somatic cells in vitro under conditions used to induce the differentiation of ES cells and produced teratomas after inoculation into mice. Furthermore, these ES-like cells formed germline chimeras when injected into blastocysts. Thus, the capacity to form multipotent cells persists in neonatal testis. The ability to derive multipotential stem cells from the neonatal testis has important implications for germ cell biology and opens the possibility of using these cells for biotechnology and medicine.

DOI： 10.1016/j.cell.2004.11.011

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論文 - 豊國 伸哉

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論文 - 豊國　伸哉