Study on the relationship between NHE and diabetic nephropathy.

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09671046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内分泌・代謝学
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: TSUDA Kinsuke Kyoto. Univ.Int.Human Sciences Professor, 総合人間学部, 教授 (10180001)
• Project Period (FY): 1997 – 1998
• Keywords: NHE (Na^+-H^+ exchanger) / gene abnormality / hypertension / diabetic nephropathy / ヒトゲノム / 糖尿病性腎症

Research Abstract

It is very important to clarify the pathogenesis and predictor of high risk for diabetic nephropathy. We have measured erythrocyte sodium-lithium-countertransport activity(SLI) which is thought to be identical sodium-proton exchanger(NHE) and our data suggest that SLC strongly reflects a predisposition to hypertension and that it can be a useful marker of diabetic nephropathy. Recently four isoforms of NHE are cloned and sequenced. We demonstrated that all NHE isoforms exist in kidney and in GK rats (type 2 diabetes model) NHE3 are expressed more than the control rats. We also clarified that NHE regulates intracellular Ca ion concentrations through Na ion. Now try to establish the system for detecting abnormality of NHE gene.

Research Products

• [Publications] J.Fujita, K.Tsuda et al.: "Nisoldipine blocks the increase of intracellular free calcium-ion concentlation associated with elevated sodium-lithium countertransport activity in RSC in patients with NIDDM" Diabetic Medicine. 14. 499-502 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] E.Mukai, K.Tsuda et al.: "Metalsolsi inhibition impaires ATP-semitive K^+ channel block by sulfonylurea in pancredtic β cells" Amor.J.Physiol (Endocrinol Metab). 274. E38-E44 (1998)
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• [Publications] A.Inada, K.Tsuda et al.: "Trancriptional represrors are increased in pancreatu is lets of Type2 diabotic raty" Biochem.Biophys.Res.Comm. 253. 712-718 (1998)
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• [Publications] T.Adachi K.Tsuda et al.: "Disorfered expression of the suirease-isonaltace complex in the small intestina in OLFTF rats, a model of non-insulin dependent diabetes mell of with insulin resistance" Biochem.Biophys.Acta. 1426. 126-132 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] R.Watanabe, K.Tsuda et al.: "The MH1 domains of Smad 2 and Smad 3 are involved in the regulition of the ALK7 signals" Biochem.Biophys.Res.Comm. 254. 707-712 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] J.Fujita, K.Tsuda et al.: "Nisoldipine improves the impaired ergtirocyti aeformatility oorrelating with elevated intracellular free calcium-ion concentration and poor glycontrol in control NIDDM" Brit J.Chin.Pharmaol. (In press).
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• [Publications] J.Fujita, K.Tsuda, H.Obayashi, I.Fukui, H.Ishida, Y.Seino: "Nisoldipine blocks the increase of intracellular free calcium-ion concentration associated with elevated sodium-lithium contertransport activity in erythrocytes in patients with NIDDM" Diabetic Medicine. 14. 499-502 (1997)
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• [Publications] E.Mukai, H.Ishida, S.kato, Y.Tsuura, S.Fujimoto, A.Ishida, M.Horie, K.Tsuda, Y.Seino: "Metabolic inhibition impairs ATP-sensitive K channel block by sulfonylurea in pancreatic beta-cells" Amer.J.Physiol.274 (1). E38-44 (1998)
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• [Publications] A.Inada, Y.Yamada, Y.Someya, A.Kubota, K.Yasuda, Y.Ihara, S.Kagimoto, A.Kuroe, K.Tsuda, Y.Seino: "Transcriptional Repressors are increased in pancreatic islets of type 2 diabetic rats." Biochem Biophys Res Comm. 253 (3). 712-718 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] R.Watanabe, Y.Yamada, Y.Ihara, Y.Someya, A.Kubota, S.Kagimoto, A.Kuroe, T.Iwakura, Z-P Shen, A.Inada, T.Adachi, N.Ban, K.Miyawaki, Y.Sunaga, K.Tsuda, Y.Seino: "The MH1 domains of Smad2 and Smad3 are involved in the regulation of the ALK7 signals." Biochem. Biophys. Res.Comm.254 (3). 707-712 (1999)
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• [Publications] T.Adachi, M.Takenoshita, H.katsura, K.Yasuda, K.Tsuda, Y.Seino, T.Enomoto, R.Yamaji, K.Miyatake, H.Inui, Y.Nakano: "Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans Tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance." Biochim. Biophys. Acta. 1426. 126-132 (1999)
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• [Publications] J.Fujita, K.Tsuda, T.Takeda, L.Yu, S.Fujimoto, M.Kajikawa, M.Nisimura, N.Mizuno, Y.Hamamoto, E.Mukai, T.Adachi, Y.Seino.: "Nisoldipine improves the impaired erythrocyte deformability correlating with elevated intracellular free calcium-ion concentration and poor glycaemic control in NIDDM" Brit.J.Clin.Pharmacol.(in press).
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