Mechanisms of insulin gene expression and regeneration of pancreatic beta-cell

2008 Fiscal Year Final Research Report

• Project/Area Number: 19591054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kagawa University
• Principal Investigator: ISHIDA Toshihiko Kagawa University, 医学部, 教授 (50159737)
• Co-Investigator(Kenkyū-buntansha): MURAO Koji 香川大学, 医学部・附属病院, 講師 (20291982) ; TOKUMITSU Hiroshi 香川大学, 医学部, 准教授 (20237077) ; IMACHI Hitomi 香川大学, 医学部・附属病院, 助教 (80380187)
• Project Period (FY): 2007 – 2008
• Keywords: インスリン / グルコース応答性 / β細胞 / glucokinase / 転写因子PREB

Research Abstract

糖尿病の病因はインスリンの作用不足であり、進行した病態では膵β細胞からのインスリン合成/分泌不全が生じる。インスリン遺伝子転写の生理的刺激は血中糖濃度の変化であり、インスリン遺伝子プロモーター内にグルコース応答領域が数カ所存在している。我々は新たな転写因子PREBがグルコース応答領域に結合してインスリン遺伝子転写を促進することを明らかにした。さらにグルコース応答に関与するglucokinaseを調節することで、膵β細胞の機能改善をおこなうことを明らかにした。

Research Products

• [Journal Article] A case of Dunnigan-type familial partial lipodystrophy (FPLD) due to lamin A/C (LMNA) mutations complicated by end-stage renal disease (2009)
  • Author(s): Imachi H, Murao K, Ohtsuka S, Fujiwara M, Muraoka T, Hosokawa H, Ishida T
  • Journal Title: Endocrine 35 Pages: 18-21
  • Peer Reviewed
• [Journal Article] A case of non-Hodgkin'slymphoma primary arising in both adrenal glands associated with adrenal failure (2009)
  • Author(s): Nishiuchi T, Imachi H, Fujiwara M, Murao K, Onishi H, Kiguchi T, Takimoto H, Kushida Y, Haba R, Ishida T
  • Journal Title: Endocrine 35 Pages: 34-37
  • Peer Reviewed
• [Journal Article] Improvement in renal dysfunction and symptoms after laparoscopic adrenalectomy in a patient with pheochromocytoma complicated by renal dysfunction (2009)
  • Author(s): Fujiwara M, Imachi H, Murao K, Muraoka T, Ohyama T, Miyai Y, Kushida Y, Haba R, Kakehi Y, Ishida T
  • Journal Title: Endocrine 35 Pages: 57-62
  • Peer Reviewed
• [Journal Article] Role of neuronal NO synthase in regulating vascular superoxide levels and mitogen-activated protein kinase phosphorylation (2009)
  • Author(s): Zhang GX, Kimura S, Murao K, Shimizu J, Matsuyoshi H, Takaki M
  • Journal Title: Cardiovasc Res 81 Pages: 389-399
  • Peer Reviewed
• [Journal Article] c-Jun N-terminal kinases inhibitor suppresses the TNF-α induced MCP-1 expression in human umbilical vein endothelial cells (2009)
  • Author(s): Ahmed RAM, Murao K, Imachi H, Yoshida K, Dobashi H, Hosomi N, Ishida T
  • Journal Title: Endocrine 35 Pages: 184-188
  • Peer Reviewed
• [Journal Article] Human scavenger receptor class type B1 is regulated by activators of peroxisome proliferators-activated receptor-γ in hepatocytes (2009)
  • Author(s): Ahmed RAM, Murao K, Imachi H, Yu X, Li J, Wong NCW, Ishida T
  • Journal Title: Endocrine 35 Pages: 233-242
  • Peer Reviewed
• [Journal Article] Tissue Doppler echocardiography for predicting arterial stiffness assessed by cardio-ankle vascular index (2009)
  • Author(s): Masugata H, Senda S, Goda F, Yamagami A, Okuyama H, Kohno T, Hosomi N, Yukiiri K, Noma T, Kiyomoto H, Murao K, Nishiyama A, Kohno M
  • Journal Title: Tohoku J Exp Med 217 Pages: 139-146
  • Peer Reviewed
• [Journal Article] Decline of plasma brain natriuretic peptide during enzyme replacement therapy in a female patient with heterozygous Fabry's disease (2009)
  • Author(s): Masugata H, Senda S, Goda F, Yamagami A, Okuyama H, Kohno T, Hosomi N, Yukiiri K, Noma T, Murao K, Kohno M, Itoh S
  • Journal Title: Tohoku J Exp Med 217 Pages: 169-174
  • Peer Reviewed
• [Journal Article] Hyperglycemia suppresses hepatic scavengerreceptor class B type I expression (2008)
  • Author(s): Murao K, Yu X, Imachi H, Cao WM, Chen K, Matsumoto K, Nishiuchi T, Wong NC, Ishida T
  • Journal Title: Am J Physiol Endocrinol Metab 294 Pages: E78-87
  • Peer Reviewed
• [Journal Article] Interferon-α decreases expression of human scavenger receptor class BI, possible HCV receptor in hepatocytes (2008)
  • Author(s): Murao K, Imachi H, Yu X, Cao WM, Nishiuchi T, Chen K, Li J, Ahmed RA, Wong NC, Ishida T
  • Journal Title: Gut 57 Pages: 664-671
  • Peer Reviewed
• [Journal Article] The Role of Calcium/Calmodulin-Dependent Protein Kinase Cascade on MIP-1α Gene Expression of ATL Cells (2008)
  • Author(s): Matsumoto K, Murao K, Imachi H, Nishiuchi T, Cao WM, Yu X, Li J, Ahmed RA, Iwama H, Kobayashi R, Tokumitsu H, Ishida T
  • Journal Title: Experimental Hematology 36 Pages: 390-400
  • Peer Reviewed
• [Journal Article] Isolated follicle-stimulating hormone (FSH) deficiency without mutation of the FSHβ gene and successful treatment with human menopausal gonadotropin (2008)
  • Author(s): Murao K, Imachi H, Muraoka T, Fujiwaha M, Kushida Y, Haba R, Ishida T
  • Journal Title: Fertil Steril 90 : 2012 Pages: e17-9
  • Peer Reviewed
• [Journal Article] ReAlignerV : web-based genomic alignment tool with high specificity and robustness estimated by species-specific insertion sequences (2008)
  • Author(s): Iwama H, Hori Y, Matsumoto K, Murao K, Ishida T
  • Journal Title: BMC Bioinformatics 9 Pages: 112-116
  • Peer Reviewed
• [Journal Article] PREB regulates transcription of pancreatic glucokinase in response to glucose and cAMP (2008)
  • Author(s): Muraoka T, Murao K, Imachi H, Yu X, Li J, Wong NC, Ishida T
  • Journal Title: J Cell Mol Med ([Epub ahead of print])
  • Peer Reviewed
• [Journal Article] The transcriptional factor prolactin regulatory element-binding protein mediates the gene transcription of adrenal scavenger receptor class BI via cAMP (2008)
  • Author(s): Murao K, Imachi H, Yu X, Cao WM, Muraoka T, Dobashi H, Hosomi N, Haba R, Iwama H, Ishida T
  • Journal Title: Endocrinology 149 Pages: 6103-6112
  • Peer Reviewed
• [Journal Article] The prolactin regulatory element-binding regulates the of 11-hydroxylase gene (2008)
  • Author(s): Imachi H, Murao K, Cao WM, Muraoka T, Nishiuchi T, Dobashi H, Hosomi N, Iwama H, Ishida T
  • Journal Title: Biochem Biophys Res Commun 376 Pages: 531-535
  • Peer Reviewed
• [Journal Article] PREB, prolactin regulatory element binding protein is involed in cAMP-mediated adiponectin gene expression in 3T3-L1 cells
  • Author(s): Li J, Murao K, Imachi H, Yu X, Muraoka T, Kim JB, Ishida T.
  • Journal Title: J Cell Mol Med
  • Peer Reviewed
• [Journal Article] Co-existence of glucagonoma with recurrent insulinoma in a patient with multiple endocrine neoplasia-type 1 (MEN-1)
  • Author(s): Nishiuchi T, Imachi H, Murao K, Fujiwara M, Muraoka T, Kikuchi F, Nishiuchi Y, Kushida Y, Haba R, Ishida T
  • Journal Title: Endocrine
  • Peer Reviewed
• [Journal Article] The transcriptional factor PREB mediates MCP-1 transcription induced by cytokines in human vascular endothelial cells
  • Author(s): Murao K, Imachi H, Yu X, Muraoka T, Hosomi N, Dobashi H, Ishida T.
  • Journal Title: Atherosclerosis
  • Peer Reviewed
• [Journal Article] Exendin-4 regulates Glucokinase expression via CaMKK/CaMKIV pathway in pancreatic β cell line
  • Author(s): Murao K, Li J, Imachi H, Muraoka T, Masugata H, Zhang GX, Kobayashi R, Ishida T, Tokumitsu H.
  • Journal Title: Diabetes Obesity & Metabolism
  • Peer Reviewed
• [Presentation] 脂肪細胞アデポネクチン発現におけるHDL受容体の役割 (2008)
  • Author(s): 村尾孝児, 井町仁美, 村岡都美江, 石田俊彦
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 20080522-24
• [Presentation] 血管内皮細胞において酸化LDLはHDL受容体発現を抑制する (2008)
  • Author(s): 井町仁美, 村尾孝児, 村岡都美江, 藤原真子, 菊池史, 石田俊彦
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 20080522-24
• [Presentation] INS-1細胞においてExenatideの作用にIslet-brain 1(IB1)が関与する (2008)
  • Author(s): 村岡都美江, 村尾孝児, 井町仁美, 藤原真子, 菊池史, 石田俊彦
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 20080522-24
• [Presentation] エリスロポイエチンのHEL細胞におけるHDL受容体CLA-1発現に及ぼす影響と作用について (2008)
  • Author(s): 西内崇将, 村尾孝児, 井町仁美, 北中則子, 村岡都美江, 西内由紀子, 松本謙介, 石田俊彦
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 20080522-24
• [Presentation] 転写因子PREBは血管平滑筋細胞におけるABC-A1遺伝子発現を増強する (2008)
  • Author(s): 村尾孝児, 井町仁美, 村岡都美江, 北中則子, 西内崇将, 石田俊彦
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 20080522-24
• [Presentation] PREB、プロラクチン調節配列結合タンパク質は3T3-L1細胞におけるcAMP媒介アディポネクチン遺伝子発現に関与する(PREB, prolactin regulatory element binding protein is involed in cAMP-mediated adiponectin gene expression in 3T3-L1 cells) (2008)
  • Author(s): 李軍華, 井町仁美, 村尾孝児, 石田俊彦
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 20080516-18
• [Presentation] INS-1細胞においてExenatideの作用にIslet-brain 1(IB1)が関与する (2008)
  • Author(s): 村岡都美江, 村尾孝児, 井町仁美, 藤原真子, 菊池史, 石田俊彦
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 20080516-18
• [Presentation] 酸化LDLによるHDL受容体発現調節について (2008)
  • Author(s): 井町仁美, 村尾孝児, 村岡都美江, 藤原真子, 石田俊彦
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 20080516-18
• [Presentation] 家族性褐色細胞腫の一例 (2008)
  • Author(s): 藤原真子, 井町仁美, 村尾孝児, 田岡利宜也, 杉元幹史, 竹林隆介, 出石邦彦, 筒井邦彦, 坂東健次, 羽場礼次, 村岡都美江, 菊池史, 筧善行, 鈴木康之, 石田俊彦
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 20080516-18
• [Presentation] チアゾリジンジオンはhepG2細胞においてヒトスカベンジャー受容体クラスBタイプI(SR-BI)発現を増強する(Thiazolidinedione increase the expression of human scavenger receptor class B type I (SR-BI) in hepG2 cells (2008)
  • Author(s): Rania Ahmed, 村尾孝児, 井町仁美, 村岡都美江, 石田俊彦
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 20080516-18
• [Presentation] 根治手術後にミトタン少量投与を開始した副腎皮質癌の1症例 (2008)
  • Author(s): 藤原真子、井町仁美、村尾孝児、村岡都美江、串田吉生、羽場礼次、石田俊彦
  • Organizer: 第8回日本内分泌学会四国支部学術集会
  • Place of Presentation: 高松
  • Year and Date: 2008-09-20
• [Presentation] ^<131>I-MIBGシンチ・FDG-PET陽性の副腎皮質腫瘍の1例 (2008)
  • Author(s): 村岡都美江、藤原真子、村尾孝児、井町仁美、菊池史、吉本卓生、祖父江理、原大雅、門田球一、串田吉生、田岡利宜也、杉元幹史、清元秀泰、羽場礼次、筧善行、石田俊彦
  • Organizer: 第8回日本内分泌学会四国支部学術集会
  • Place of Presentation: 高松
  • Year and Date: 2008-09-20
• [Presentation] 胸腺ナース細胞から副甲状腺細胞への分化誘導の試み (2008)
  • Author(s): 村尾孝児、井町仁美、村岡都美江、西内崇将、藤原真子、土橋浩章、石田俊彦
  • Organizer: 第8回日本内分泌学会四国支部学術集会
  • Place of Presentation: 高松
  • Year and Date: 2008-09-20
• [Presentation] 遅発型糖原病II型の1症例 (2008)
  • Author(s): 菊池史、村岡都美江、藤原真子、村尾孝児、井町仁美、島村美恵子、出口一志、正木勉、石田俊彦
  • Organizer: 第8回日本内分泌学会四国支部学術集会
  • Place of Presentation: 高松
  • Year and Date: 2008-09-20
• [Presentation] 抗GAD抗体陽性の妊娠糖尿病の一例 (2008)
  • Author(s): 井町仁美、菊池史、村尾孝児、村岡都美江、藤原真子、吉本卓生、森信博、田中宏和、石田俊彦
  • Organizer: 第8回日本内分泌学会四国支部学術集会
  • Place of Presentation: 高松
  • Year and Date: 2008-09-20
• [Presentation] 研究奨励賞受賞講演 : High-density lipoprotein(HDL)受容体(scavenger receptor class BI/CLA-1)の同定および臨床的機能解析 (2008)
  • Author(s): 村尾孝児
  • Organizer: 第81回 日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-18
• [Presentation] 血管内皮細胞におけるHDL受容体SR-BI/CLA-1を介するeNOSの活性化に与える代謝性因子の影響 (2008)
  • Author(s): 村尾孝児, 井町仁美, 村岡都美江, 北中則子, 李軍華, 藤原真子, 陳可, Rania A.M. Ahmed, 石田俊彦
  • Organizer: 第9回糖尿病合併症とVascular Biology研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-01
• [Book] 糖尿病学の進歩2008 (2008)
  • Author(s): 村尾孝児、井町仁美、村岡都美江、石田俊彦
  • Total Pages: 83-87
  • Publisher: 診断と治療社