Faculty Profiles - ASAKAWA Akihiro

Papers - ASAKAWA Akihiro

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Inui Akio, Asakawa Akihiro . Feeding and Gastrointestinal Motility : Regulation by Ghrelin Gene Products(Symposium : Frontiers Research and Practice in Psychosomatic Medicine) . Japanese Journal of Psychosomatic Medicine48 ( 7 ) 625 - 630 2008

Language：Japanese Publisher：Japanese Society of Psychosomatic Medicine

Gastrointestinal (GI) hormones are well known to be important regulators not only in GI functions but also in feeding behavior. Ghrelin, a motilin-related family of regulatory peptide from the stomach, is the recent addition of this list, which has a charactelistic n-octanoylated serine at position 3. In addition to its ability to stimulate growth hormone (GH) secretion, ghrelin increases appetite and gastric motility/emptying and induces a positive energy balance leading to body weight gain. Ghrelin is a complementary, yet antagonistic, signal to leptin reflecting acute and chronic changes in energy balance, the effects of which are mediated by hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP). Ghrelin induces the fasted pattern of gastroduodenal motility (phase III or hunger contractions) , and the ghrelin-NPY axis is involved in the physiological occurrence of the interdigestive phase III contractions in rodents. On the other hand, desacyl form of ghrelin that accounts for approximately 90% of total circulating ghrelin, decreases food intake and gastric emptying, and disrupts the fasted pattern of gastric motility. Obestatin, a recently identified ghrelin gene product, may also act inhibitory in appetite and GI motility regulation although much more controversial than ghrelin. The findings suggest that ghrelin gene products may differently regulate appetite and gastrointestinal motility through different endocrine/neural pathways along the gut-brain axis.

DOI： 10.15064/jjpm.48.7_625

CiNii Research

藤宮峯子, 浅川明弘, 乾明夫 . 【脳腸ペプチド】グレリンと腸-脳相関 . 医学のあゆみ223 ( 7 ) 549 - 553 2007.11

Publisher：医歯薬出版(株)

肥満症、糖尿病、消化管機能異常症(FGIDs)は、先進国で人口の1〜2割に達する重要な疾患である。過食を防ぐことは肥満症や糖尿病の予防につながるため、これまで摂食に関連する脳腸ペプチドの研究が活発に行われてきた。摂食と消化管運動は密接に関連しており、視床下部の神経ペプチドによって制御されている。グレリンは末梢から出て視床下部に作用し、摂食行動と消化管運動を変化させる代表的なペプチドであり、グレリンを中心にした腸-脳相関を知ることは、上記疾患の治療に直結すると考えられる。(著者抄録)

浅川明弘, 藤宮峯子, 乾明夫 . 【脳腸ペプチド】PYYとPPの基礎と臨床 . 医学のあゆみ223 ( 7 ) 529 - 532 2007.11

Publisher：医歯薬出版(株)

Peptide YY(PYY)およびpancreatic polypeptide(PP)は、neuropeptide Y(NPY)とともにPP familyを形成し、受容体にはY1,Y2,Y4,Y5,y6の1つのサブタイプが存在している。末梢のPYYおよびPPは迷走神経を介して視床下部にシグナル伝達し、摂食調節ペプチドを駆動させ、摂食を抑制する。肥満においては血中PYYおよびPPは低値、やせにおいては高値を示し、運動は血中のPYY,PPを上昇させる。これらは、PYY,PPが肥満ややせの予防や治療のターゲットになる可能性を示唆している。(著者抄録)

Huang L, Toyoshima M, Asakawa A, Inoue K, Harada K, Kinoshita T, Koizumi A . Roles of neuropeptides in O,O,S-trimethylphosphorothioate (OOS-TMP)-induced anorexia in mice. . Biochemical and biophysical research communications362 ( 1 ) 177 - 182 2007.10Reviewed

Ueno N. . Blunted metabolic response to fasting in obese mice . Endocrine32 ( 2 ) 192 - 196 2007.10Reviewed

Yuzuriha H. . Gastrointestinal hormones (anorexigenic peptide YY and orexigenic ghrelin) influence neural tube development . FASEB Journal21 ( 9 ) 2108 - 2112 2007.7Reviewed

Ueno N. . Increased circulating cholecystokinin contributes to anorexia and anxiety behavior in mice overexpressing pancreatic polypeptide . Regulatory Peptides141 ( 1-3 ) 8 - 11 2007.6Reviewed

Asakawa A, Toyoshima M, Fujimiya M, Harada K, Ataka K, Inoue K, Koizumi A . Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus. . International journal of molecular medicine19 ( 5 ) 733 - 9 2007.5Reviewed

Asakawa A, Toyoshima M, Inoue K, Koizumi A . Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system. . International journal of molecular medicine19 ( 4 ) 649 - 52 2007.4Reviewed

Asakawa A., Toyoshima M., Inoue K., Koizumi A. . Ins2<sup>Akita</sup> mice exhibit hyperphagia and anxiety behavior via the melanocortin system . International Journal of Molecular Medicine19 ( 4 ) 649 - 652 2007.4

Language：Japanese Publisher：International Journal of Molecular Medicine

Elevated anxiety symptoms have been reported to be present in many patients with diabetes mellitus. The underlying mechanisms by which diabetes mellitus influences behavior remain to be determined. We assessed feeding and anxiety behaviors in spontaneously diabetic Ins2Akita mice. We measured blood glucose, body weight, and food and water intakes in C57BL/6 heterozygote Ins2Akita mice. The behavioral properties of Ins2Akita mice were assessed in an open-field test and an elevated plus-maze. The gene expression of hypothalamic neuropeptides was examined in non-food-deprived Ins2Akita mice. Body weights of the Ins2Akita mice were less than those of the age-matched C57BL/6 mice, as controls. Food and water intakes were increased in the Ins2Akita mice. In the open-field test, the Ins2Akita mice had decreased locomotor activity and increased immobilization time. The Ins2Akita mice exhibited anxiety behavior in the elevated plus-maze. RT-PCR analysis showed decreased proopiomelanocortin (POMC) mRNA expression and increased agouti-related protein (AGRP) mRNA expression in Ins2Akita mice. There were no significant differences in hypothalamic ghrelin mRNA expression. These observations indicate that Ins2Akita mice, which are characterized by hypoinsulinemia and hyperglycemia, exhibited hyperphagia and anxiety behavior; the mechanism of action involved the activation of hypothalamic AGRP and the inactivation of hypothalamic POMC. In addition, Ins2Akita mice are a useful model for understanding the mechanisms involved in the psychological complications of diabetes mellitus. Further, melanocortin systems may be therapeutic targets not only for diabetes but also for its associated complications.

DOI： 10.3892/ijmm.19.4.649

Scopus

Kojima S. . A role for pancreatic polypeptide in feeding and body weight regulation . Peptides28 ( 2 ) 459 - 463 2007.2Reviewed

Toyoshima M, Asakawa A, Fujimiya M, Inoue K, Inoue S, Kinboshi M, Koizumi A . Dimorphic gene expression patterns of anorexigenic and orexigenic peptides in hypothalamus account male and female hyperphagia in Akita type 1 diabetic mice. . Biochemical and biophysical research communications352 ( 3 ) 703 - 8 2007.1Reviewed

浅川明弘, 藤宮峯子, 乾明夫 . 【消化管の動きをコントロールするもの　その不調は疾患が原因か?】グレリンは消化管運動にどのような影響を及ぼすか? . 分子消化器病3 ( 4 ) 311 - 315 2006.12

浅川明弘, 藤宮峯子, 乾明夫 . 【機能性消化器疾患の基礎と臨床】脳腸相関におけるグレリンの役割 . 消化器科43 ( 6 ) 493 - 497 2006.12

Inui T. . HER-2 overexpression and targeted treatment by trastuzumab in a very old patient with gastric cancer . Journal of Internal Medicine260 ( 5 ) 484 - 487 2006.11Reviewed

浅川明弘, 藤宮峯子, 乾明夫 . 【消化管運動の基礎　胃癌手術における生理学の重要性】消化管運動と消化管ホルモン　グレリン,モチリンを中心に . G.I.Research14 ( 3 ) 246 - 252 2006.6Reviewed

Publisher：(株)先端医学社

モチリンは十二指腸を中心とした消化管に存在し,空腹期において消化管の平滑筋に対して直接,あるいは迷走神経を介して作用し,胃からはじまり順次回腸に向けて伝播していく,一連の強力な収縮運動に関与している.1999年に成長ホルモン放出促進因子レセプター(GHS-R)の内因性リガンドであるグレリンが胃から同定された.グレリンは28個のアミノ酸よりなるペプチドで,脂肪酸による修飾を特徴としている.グレリンとそのレセプターは,モチリンおよびそのレセプターとの間での構造上の相同性が高く,グレリンが新たなモチリンペプチドファミリーの一員であることが示唆される.空腹期のグレリンの投与は,胃前庭部,十二指腸における空腹期強収縮運動の頻度を増加させるとともに,食後期の投与は,収縮波を空腹期のパターンに変化させる.一方,脂肪酸による修飾のないデスアシルグレリンの投与は,脂肪酸によって修飾されたグレリンとは逆に上部消化管の空腹期強収縮運動の頻度を抑制する.グレリンの消化管運動調節作用は,グレリンおよびそのレセプターが消化管運動異常に関係する,さまざまな疾患に対しての創薬のターゲットとなる可能性を示唆している(著者抄録)

浅川明弘, 藤宮峯子, 乾明夫 . S1-1.ホルモンからのアプローチ(消化管機能研究の新しい視点,シンポジウム1,第48回日本平滑筋学会総会) . 日本平滑筋学会雑誌10 ( 1 ) "J - 5" 2006.4

藤宮峯子, 浅川明弘, 乾明夫 . 【消化器疾患　state of arts　消化管(食道・胃・腸)】病態生理の基礎的・臨床的研究の進歩　消化管運動　グレリン,デスアシルグレリンによる消化管運動の制御と脳腸相関 . 医学のあゆみ別冊 ( 消化器疾患Ver.3 ) 5 - 9 2006.4

Fujimiya M. . Acylated ghrelin and des-acyl ghrelin exert different effects on the gastrointestinal motility in conscious rats . International Congress Series1287 361 - 367 2006.4Reviewed

Inoue H. . Role of hepatic STAT3 in brain-insulin action on hepatic glucose production . Cell Metabolism3 ( 4 ) 267 - 275 2006.4Reviewed

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Papers - ASAKAWA Akihiro