| Co-Investigator(Kenkyū-buntansha) |
MORII Hirotoshi OSAKA CITY UNIVERSITY MEDICAL SCHOOL SECOND DEPARTMENT OF INTERNAL MEDICINE PROF, 医学部, 教授 (40046983)
KAWAGISHI Takahiko OSAKA CITY UNIVERSITY MEDICAL SCHOOL SECOND DEPARTMENT OF INTERNAL MEDICINE RESE, 医学部, 助手 (60224739)
SHOJI Shigeichi OSAKA CITY UNIVERSITY MEDICAL SCHOOL SECOND DEPARTMENT OF INTERNAL MEDICINE EX-R, 医学部, 助手 (50162748)
INABA Masaaki OSAKA CITY UNIVERSITY MEDICAL SCHOOL SECOND DEPARTMENT OF INTERNAL MEDICINE ASSI, 医学部, 講師 (00176405)
NISHIZAWA Yoshiki OSAKA CITY UNIVERSITY MEDICAL SCHOOL SECOND DEPARTMENT OF INTERNAL MEDICINE ASSO, 医学部, 助教授 (00128745)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
[Background and Aim] In the early stage of diabetes mellitus, it is known that functional abnormalities ofrenal tubuli is present and may related to diabetic osteopenia. In this study, we examine metabolic abnormalities of phosphate, vitamin D and parathyroid hormone in diabetic renal tubuli, using molecular biological methods in GK rats (an animal model of type II diabetes mellitus) and OK cells (proximal tubular epithelial cell line of opossum kidney). We further extend the research ot the related field in early stage of diabetes mellitus.
[Results] 1.Gene expression of vitamin D receptor and 24 hydroxylase in OK cells. With the method of RT-PCR and Northern blotting, we demonstrated, for the first time, gene expression of vitamin D receptor and 24 hydroxylase in OK cells. 24-hydroxylase gene expression was up-regul ated by stimulation with 1,25 dihydroxy vitamin D,but not with 1-34 parathyroid hormone. (Eiji Ishimura, et al. FEBS lett 337,48-51,1994.). 2.Impaired phosphate handling i
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n renal tubuli of GK rats. Under parathyroidectomy, urinary phosphate excretion was significantly higher in GK rats than in Wistar rats at any infused phosphate concentration (0-40mM). Infusion of 1-34 parathyroid hormone (2.5U/hour), urinary excretion of phoshpate and cAMP was significantly higher in GK rats than in Wistar rats. (Eiji Ishimura, et al. Deabetes Res 23 : 153-160,1993.) 3. Impaired vitamin D metabolism and response in GK rats. Serum concentration of 1,25 dihydroxyvitamin D was significantly higher and that of 24,25 dihydoroxyvitamin D was significantly lower in GK rats than in Wistar rats. In GK rats, compared to Wistar rats, gene expression of 24-hydroxylase expression was significantly increased by the stimulation with 1,25dihydroxyvitamin D.(Eiji Ishimura et al.Miner Electrolyte Met ab 21 : 205-210,1995) 4.Effect of high glucose on OK cells. OK cells were cultured in either 50 mM or 5 mM glucose condition. Fifteen min. after the stimulation of 1-34 PTH,the levels of medium cAMP concentration was higher in the former condition than in the latter. There was no significant difference in 24-hydoroxylase gene expression after 1,25 dihydoroxyvitamin D stimulation in either condition. 5.Related research. High glucose condition reduced osteocalcin protein production and gene expression in osteoblastic cell line, MG 63. Vitamin Dreceptor number was reduced under this condition (M.Inaba et al.J Bone Miner Res 10 : 1050-1056,1995.). In the study of hyperinsulinemic euglycemic clamp in human NIDDM subjects, responsiveness of insulin was reduced in patients with renal insufficiency. (Eiji Ishimura, et al.Metabolism 1996 (in press)) Less
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