2000 Fiscal Year Annual Research Report

肝インスリン抵抗性発現に関与する糖新生系律速酵素遺伝子転写因子の解明

Research Project

Project/Area Number	11671115
Research Institution	Osaka University
Principal Investigator	山崎知行大阪大学, 医学部, 助手 (00303975)
Co-Investigator(Kenkyū-buntansha)	河野典夫大阪大学, 医学部, 教授 (30093412)
Keywords	糖新生系 / ホスホエノールピルビン酸カルボキシキナーゼ / クローニング / 糖尿病
Research Abstract	1.ヒトミトコンドリア型ホスホエノールピルビン酸カルボキシキナーゼ(PCK-2)遺伝子プロモーター領域のクローニングすでに報告されている遺伝子の配列を用いて第1エキソンから第2イントロンにかけ増幅するプライマーを作成した。このプライマーによりPCR法を用いて1.2x10^5クローンのPACライブラリーのスクリーニングを行い2つのクローンを得た。これらはオーバーラップしており、PCK-2のプロモーター領域を含んでいるものと考えられた。同領域の塩基配列を決定するとともに。、転写開始点を決定した。また、同領域を用いたレポーター分析を行いプロモーター活性の存在を確認した。これらの成果については現在英文学術雑誌に発表準備中である。 2.糖尿病患者におけるHepatocyte Nuclear Factor-1(HNF-1)遺伝子の解析糖尿病の原因遺伝子の異常を解明するために、糖尿病患者におけるヒトHNF-1α遺伝子配列について解析を行い、新たに2つの遺伝子異常を明らかにした。 3.糖新生系酵素の過剰発現によるβ細胞機能障害に関する検討糖新生系酵素の過剰発現が膵β細胞機能に与える影響を検討するため、マウスβ細胞株であるMIN6を用いてグルコース-6-ホスファターゼを過剰発現するβ細胞株を樹立した。この細胞株ではコントロールに比してグルコース応答性のインスリン分泌が傷害されていた。 4.ラットPCK-1遺伝子プロモーターのインスリンによる転写制御ラットPCK-1遺伝子プロモーターのインスリンによる転写制御について転写因子FKHRとの関連性に関する検討を行った。

Research Products
(23 results)

All Other

All Publications (23 results)

[Publications] H.Iwahashi, et al.: "Emerging therapeutic strategies in autoimmune diabetes : etiology, prediction, prevention and cure."Emerging Therapeutic Targets. 3・1. 177-193 (1999)
[Publications] M.Kuwajima et.al.: "Cardiomegaly in the juvenile visceral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection."FEBS Lett. 443・3. 261-266 (1999)
[Publications] Y.Terauchi, et.al.: "Increased insulin sensitivity and hypoglycaemina in mice lacking the p85 subunit of phosphoinositide 3-kinase."Nature Genet.. 21・2. 230-235 (1999)
[Publications] A.Imagawa, et.al.: "Immunological abanormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus."Diabetelogia. 42・5. 574-578 (1999)
[Publications] I.Yoshiuchi, et.al.: "Three new mutations in the hepatocyte nuclear factor-la gene in Japanese subjects with diabetes mellitus : Clinicla features and functional characterization."Diabetologia. 42・5. 621-626 (1999)
[Publications] R.Hamaoka, et.al.: "Different expression patterns of nitric oxidase synthase isozymes in various gynecological cancers."J.Cancer Res.Clin.Oncol.. 125・6. 321-326 (1999)
[Publications] R.Hamaoka, et.al.: "Overexpression of the aldose reductase gene induces apoptosis in pancreatic b-cells by causing a redox imbalance."J.Biochem.. 126・1. 41-47 (1999)
[Publications] K.Okita, et.al.: "Human insulin gene is a target gene of hepatocyte nuclear factor-1α (HNF-1α) and HNF-1β."Biochem.Biophys.Res.Commun.. 263・2. 566-569 (1999)
[Publications] T.Oue, et.al.: "Risk factors for the progression of microalbuminuria in Japanese type 2 diabetic patients - a 10-year follow-up study."Diab.Res.Clin.Prac.. 46・1. 47-55 (1999)
[Publications] M.Moriwaki, et.al.: "Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with resent-onset Type I diabetes mellitus."Diabetelogia. 42・11. 1332-1340 (1999)
[Publications] H.Kaneto et.al.: "Antioxidant treatment protects pancreatic b-cells against glucose toxicity in C57BL/Ksj-db/db mouse."Diabetes. 48・12. 2398-2406 (1999)
[Publications] J.Miyagawa, et.al.: "Immunohisochemical localization of Betacellulin, a new member of EGF family, in normal human pancreas and islet tumor cells."Endocrine J.. 46・6. 755-764 (1999)
[Publications] Q.Yang, et.al.: "Structure/function studies of hepatocyte nuclear factor-1α, a diatetes-associated transcription factor."Biochem.Biophys.Res.Commun.. 266・1. 196-202 (1999)
[Publications] A.Imagawa et.al.: "A novel subtype of Type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies."New Engl.J.Med.. 342・5. 301-307 (2000)
[Publications] K.Iizuka, et.al.: "Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta cell line"J.Endocrinol.. 164・3. 307-314 (2000)
[Publications] R.K.Hall et al.: "Regulation of Phosphoenolpyruvate Carboxykinase and Insulin-like Growth Factor-binding Protein-1 Gene Expression by Insulin THE ROLE OF WINGED HELIX/FORKHEAD PROTEINS"J.Biol.Chem.. 275・39. 30169-30175 (2000)
[Publications] 河野典夫: "内科学書"中山書店. 2191 (1999)
[Publications] 河野典夫,山崎知行: "消化器疾患-state of arts II 肝・胆・膵"医歯薬出版. 562 (1999)
[Publications] 河野典夫: "内科学"朝倉書店. 2110 (1999)
[Publications] 山崎知行: "広範囲血液・尿化学検査、免疫学的検査(1)ムその数値をどう読むか"日本臨床社. 662 (1999)
[Publications] 河野典夫: "総合内科診断学"朝倉書店. 626 (2000)
[Publications] 河野典夫: "糖尿病、高脂血症、コ・メディカルのための病態生理アトラス"文光堂. 216 (2000)
[Publications] 河野典夫: "イヤーノートSelected articles 2001"メディックメディア. 1619 (2000)

2000 Fiscal Year Annual Research Report

肝インスリン抵抗性発現に関与する糖新生系律速酵素遺伝子転写因子の解明

Principal Investigator

山崎 知行 大阪大学, 医学部, 助手 (00303975)

Research Products

[Publications] H.Iwahashi, et al.: "Emerging therapeutic strategies in autoimmune diabetes : etiology, prediction, prevention and cure."Emerging Therapeutic Targets. 3・1. 177-193 (1999)

[Publications] M.Kuwajima et.al.: "Cardiomegaly in the juvenile visceral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection."FEBS Lett. 443・3. 261-266 (1999)

[Publications] Y.Terauchi, et.al.: "Increased insulin sensitivity and hypoglycaemina in mice lacking the p85 subunit of phosphoinositide 3-kinase."Nature Genet.. 21・2. 230-235 (1999)

[Publications] A.Imagawa, et.al.: "Immunological abanormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus."Diabetelogia. 42・5. 574-578 (1999)

[Publications] I.Yoshiuchi, et.al.: "Three new mutations in the hepatocyte nuclear factor-la gene in Japanese subjects with diabetes mellitus : Clinicla features and functional characterization."Diabetologia. 42・5. 621-626 (1999)

[Publications] R.Hamaoka, et.al.: "Different expression patterns of nitric oxidase synthase isozymes in various gynecological cancers."J.Cancer Res.Clin.Oncol.. 125・6. 321-326 (1999)

[Publications] R.Hamaoka, et.al.: "Overexpression of the aldose reductase gene induces apoptosis in pancreatic b-cells by causing a redox imbalance."J.Biochem.. 126・1. 41-47 (1999)

[Publications] K.Okita, et.al.: "Human insulin gene is a target gene of hepatocyte nuclear factor-1α (HNF-1α) and HNF-1β."Biochem.Biophys.Res.Commun.. 263・2. 566-569 (1999)

[Publications] T.Oue, et.al.: "Risk factors for the progression of microalbuminuria in Japanese type 2 diabetic patients - a 10-year follow-up study."Diab.Res.Clin.Prac.. 46・1. 47-55 (1999)

[Publications] M.Moriwaki, et.al.: "Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with resent-onset Type I diabetes mellitus."Diabetelogia. 42・11. 1332-1340 (1999)

[Publications] H.Kaneto et.al.: "Antioxidant treatment protects pancreatic b-cells against glucose toxicity in C57BL/Ksj-db/db mouse."Diabetes. 48・12. 2398-2406 (1999)

[Publications] J.Miyagawa, et.al.: "Immunohisochemical localization of Betacellulin, a new member of EGF family, in normal human pancreas and islet tumor cells."Endocrine J.. 46・6. 755-764 (1999)

[Publications] Q.Yang, et.al.: "Structure/function studies of hepatocyte nuclear factor-1α, a diatetes-associated transcription factor."Biochem.Biophys.Res.Commun.. 266・1. 196-202 (1999)

[Publications] A.Imagawa et.al.: "A novel subtype of Type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies."New Engl.J.Med.. 342・5. 301-307 (2000)

[Publications] K.Iizuka, et.al.: "Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta cell line"J.Endocrinol.. 164・3. 307-314 (2000)

[Publications] R.K.Hall et al.: "Regulation of Phosphoenolpyruvate Carboxykinase and Insulin-like Growth Factor-binding Protein-1 Gene Expression by Insulin THE ROLE OF WINGED HELIX/FORKHEAD PROTEINS"J.Biol.Chem.. 275・39. 30169-30175 (2000)

[Publications] 河野典夫: "内科学書"中山書店. 2191 (1999)

[Publications] 河野典夫,山崎知行: "消化器疾患-state of arts II 肝・胆・膵"医歯薬出版. 562 (1999)

[Publications] 河野典夫: "内科学"朝倉書店. 2110 (1999)

[Publications] 山崎知行: "広範囲血液・尿化学検査、免疫学的検査(1)ムその数値をどう読むか"日本臨床社. 662 (1999)

[Publications] 河野典夫: "総合内科診断学"朝倉書店. 626 (2000)

[Publications] 河野典夫: "糖尿病、高脂血症、コ・メディカルのための病態生理アトラス"文光堂. 216 (2000)

[Publications] 河野典夫: "イヤーノートSelected articles 2001"メディックメディア. 1619 (2000)

山崎知行大阪大学, 医学部, 助手 (00303975)