丸山 圭介 (マルヤマ ケイスケ)

MARUYAMA Keisuke

写真a

職名

准教授

専門分野(科研費分類) 【 表示 / 非表示

  • 内分泌学

 

論文 【 表示 / 非表示

  • Neuromedin U suppresses prolactin secretion via dopamine neurons of the arcuate nucleus

    Nakahara K., Maruyama K., Ensho T., Mori K., Miyazato M., Kangawa K., Uemura R., Sakoda H., Nakazato M., Murakami N.

    Biochemical and Biophysical Research Communications   521 ( 2 ) 521 - 526   2020年01月  [査読有り]

    共著

     概要を見る

    © 2019 Neuromedin U (NMU) has a precursor that contains one additional peptide consisting of 33 or 36 amino acid residues. Recently, we identified this second peptide from rat brain and designated it neuromedin U precursor-related peptide (NURP), showing it to stimulate prolactin release from the pituitary when injected via the intracerebroventricular (icv) route. Here, we examined whether NMU, like NURP, also stimulates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pituitary. This suppression of prolactin release by NMU was observed in hyper-prolactin states such as lactation, stress, pseudopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. Immunohistochemical analysis revealed that icv injection of NMU induced cFos expression in dopaminergic neurons of the arcuate nucleus, but not the substantia nigra. Mice with double knockout of NMU and neuromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These results suggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.

    DOI PubMed

  • Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents

    Islam M., Mita Y., Maruyama K., Tanida R., Zhang W., Sakoda H., Nakazato M.

    The Journal of endocrinology   244 ( 1 ) 13 - 23   2020年01月  [査読有り]

    共著

     概要を見る

    Ghrelin, a stomach-derived peptide, promotes feeding and growth hormone (GH) secretion. A recent study identified liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inhibitor of ghrelin-induced GH secretion, but the effect of LEAP2 in the brain remained unknown. In this study, we showed that intracerebroventricular (i.c.v.) administration of LEAP2 to rats suppressed central ghrelin functions including Fos expression in the hypothalamic nuclei, promotion of food intake, blood glucose elevation, and body temperature reduction. LEAP2 did not inhibit neuropeptide Y (NPY)-induced food intake or des-acyl ghrelin-induced reduction in body temperature, indicating that the inhibitory effects of LEAP2 were specific for GHSR. Plasma LEAP2 levels varied according to feeding status and seemed to be dependent on the hepatic Leap2 expression. Furthermore, ghrelin suppressed the expression of hepatic Leap2 via AMPK activation. Together, these results reveal that LEAP2 inhibits central ghrelin functions and crosstalk between liver and stomach.

    DOI PubMed

  • Purification and identification of native forms of goldfish neuromedin U from brain and gut

    Maruyama K., Kaiya H., Miyazato M., Murakami N., Nakahara K., Matsuda K.

    Biochemical and Biophysical Research Communications   517 ( 3 ) 433 - 438   2019年09月  [査読有り]

    共著

     概要を見る

    © 2019 Neuromedin U (NMU) plays important roles in energy homeostasis in rodents and birds. Previously, our group has isolated four cDNAs encoding precursor proteins of NMU from the goldfish brain and gut, and it was assumed that these transcripts are produced by alternative splicing. We have also demonstrated that intracerebroventricular (ICV) injection of putative goldfish NMU inhibits food intake. However, as native goldfish NMU has not yet been identified, we attempted to purify it from goldfish brain and gut extracts. To assess NMU activity in fractions at each purification step, we measured changes in the intracellular concentrations of Ca2+ using HEK293 cells expressing goldfish NMU-R1 or -R2. We isolated a 25-amino-acid peptide (NMU-25) from the brain and gut and found that its primary structure is similar to that of mammalian NMU. Another 21-amino-acid peptide (NMU-21) was purified from the brain, but not from the gut. Furthermore, a 9-amino-acid peptide (NMU-9) identical to the C-terminus of NMU-21 and -25 was also isolated from the brain and gut. Treatment with synthetic NMU-9, -21 and -25 dose-dependently increased the intracellular Ca2+ concentration in mammalian cells expressing goldfish NMU-R1 and -R2. We also examined the effect of ICV-administered synthetic goldfish NMUs on goldfish food intake. NMU-25 inhibited food intake to the same degree as NMU-21. However, the inhibitory effect of NMU-9 was slightly weaker than those of NMU-21 and -25. These results indicate that several molecular forms of NMU exist in the goldfish brain and gut, and that all of them play physiological roles via NMU-R1 and NMU-R2.

    DOI PubMed

  • Comparison of glucose tolerance between wild-type mice and mice with double knockout of neuromedin U and neuromedin S

    Ensho T., Maruyama K., Qattali A., Yasuda M., Uemura R., Murakami N., Nakahara K.

    Journal of Veterinary Medical Science   81 ( 9 ) 1305 - 1312   2019年09月  [査読有り]

    共著

     概要を見る

    © 2019 The Japanese Society of Veterinary Science. Recently, it has been proposed that neuromedin U (NMU) is “decretin”, which suppresses insulin secretion from the pancreas in vitro. Here we examined the possible involvement of NMU in insulin secretion in vivo by comparing the plasma glucose and insulin levels of wild-type mice with those of double knockout (D-KO) of the NMU and neuromedin S (NMS) genes, as NMS binds to the neuromedin U receptor. If NMU is, in fact, “decretin”, which inhibits insulin secretion from the pancreas, then NMU-deficient mice might result in higher plasma insulin levels than is the case in wild-type mice, or injection of NMU lead to suppression of plasma insulin level. In this study, we found that the fasting plasma level of insulin was not increased in D-KO mice. Glucose tolerance tests revealed no significant difference in plasma insulin levels between wild-type mice and D-KO mice under non-fasting conditions. After peripheral injection of NMU, plasma glucose and insulin levels did not show any significant changes in either wild-type or D-KO mice. Glucose tolerance testing after 3 weeks of high fat feeding revealed no significant difference in plasma insulin levels during 60 min after glucose injection between wild-type and D-KO mice. These results suggest that even if NMU is a decretin candidate, its physiological involvement in suppression of insulin secretion may be very minor in vivo.

    DOI PubMed CiNii

  • Neuromedin U precursor-related peptide (NURP) exerts neuromedin U-like sympathetic nerve action in the rat

    Ensho T., Maruyama K., Mori K., Miyazato M., Kangawa K., Nakahara K., Murakami N.

    Biochemical and Biophysical Research Communications   492 ( 3 ) 412 - 418   2017年10月  [査読有り]

    共著

     概要を見る

    © 2017 It has been suggested that novel peptide that is produced from the neuromedin U (NMU) precursor may exist, as this precursor contains multiple consensus sequences for proteolytic processing. Recently, we identified two mature novel peptides comprising 33 and 36 residues in the rat brain, which were designated neuromedin U precursor-related peptide (NURP) 33 and 36. In the present study, we compared the roles of NURP33 and 36 with that of NMU, as neither activates the NMU receptors. Immunoreactivity for NMU and NURPs was widely present in the central nervous system and showed a similar distribution. Intracerebroventricular (icv) injection of NURP33 in rats increased locomotor activity, energy expenditure, heart rate and back surface temperature (BS-T), similarly to NMU or NURP36. NMU treatment reduced food intake, but NURP33 did not. Pretreatment with the β3 blocker, SR59230A, and the cyclooxygenase blocker, indomethacin, inhibited the NURP33- or NMU-induced increase of BS-T. In addition, icv injection of NURP33 or NMU increased the expression of mRNA for cyclooxygenase 2 in the hypothalamus and for uncoupling protein 1 in the brown adipose tissue. These results suggest that although NURP33 and 36 do not activate the NMU receptors, they might exert NMU-like sympathetic nerve action in the brain.

    DOI PubMed

全件表示 >>

著書 【 表示 / 非表示

  • 肥満外科モデル動物の作製と意義 最新肥満症学

    宮澤崇、丸山圭介、山下貴裕 (担当: 共著 )

    日本臨牀社  2014年05月

科研費(文科省・学振)獲得実績 【 表示 / 非表示

  • NMUとの機能的連関に着目した、新規ペプチドホルモンNURPの生理機能の解明

    基盤研究(C)

    研究期間:  2019年  -  2022年03月  代表者:  丸山圭介

  • 肥満減量手術モデルラットの消化管から分泌される機能性タンパク質の生理機能の解明

    若手研究(B)

    研究期間:  2016年04月  -  2019年03月  代表者:  丸山圭介

  • 新たに見出されたNMU/NMS関連ホルモンの視床下部における生理機能の探索

    若手研究(B)

    研究期間:  2013年04月  -  2016年03月  代表者:  丸山圭介

  • 魚類の摂食行動を抑制する脳制御機構に関する研究

    特別研究員推奨費

    研究期間:  2007年04月  -  2010年03月  代表者:  丸山圭介

研究発表 【 表示 / 非表示

  • ニューロメジンS前駆体中の新規ペプチド(NSRP)の生理機能の探索

    田口 史門、延生 卓也、森 健二、宮里 幹也、寒川 賢治、丸山 圭介、村上 昇、中原 桂子

    第162回日本獣医学会学術集会  (茨城県つくば市 つくば国際会議場)  2019年09月  -  2019年09月    日本獣医学会