| Project/Area Number |
63480271
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
KONO Norio Osaka University Medical School, assistant Professor, 医学部, 講師 (30093412)
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| Co-Investigator(Kenkyū-buntansha) |
KAWACHI Masanori Osaka University Medical School, Research associate, 医学部附属病院, 医員
YAMADA Yuya Osaka University Medical School, Research associate, 医学部附属病院, 医員
SHIMIZU Takao Osaka University Medical School, Instructor, 医学部, 助手 (40206199)
KUWAJIMA Masamichi Osaka University Medical School, Instructor, 医学部, 助手 (00205262)
篠村 恭久 大阪大学, 医学部, 助手 (90162619)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1988: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Unicacid / Hypoxanthine / Glycogenosis / Hyperunicemia / Myopathy / Exercise / オキシプリン / 筋原性高尿酸血症 / プリン体代謝 / ミオパチー / グリコーゲン病 / ミトコンドリア脳筋症 / 甲状腺機能低下症 / 電解質異常 / 運動負荷試験 |
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| Research Abstract |
We reported exertional hyperuricemia occurs in muscle glycogenosis types III, V and VII. When muscle energy production does not fill its requirement for continuing exercise, purine nucleotide deiradation is accelerated in working muscles. Its degradative metabolites, such as inosine, hypoxanthine, and ammonia are released into blood stream. Inosine and hypoxanthine are taken up by liver and metabolized to uric acid. We have classified this novel type of hyperuricemia as "myogenic hyperuricemis".
We studied whether myogenic hyperuricemia occurs in other myopadiic diseases. Excess muscle purine degradation is observed on exertion in patients with hypoparathyroidism and in some patients with hypopotassemia or with hypothyroidism, whereas it is not in patients with drug-induced myopathy, polymyositis, or hypercalcemia. Aerobic exercise, not anaerobic exercise, enhances muscular adenine nucleotide degradation in Keams-Sayre syndrome, in which syndrome it is mitochondrial metabolism that is impaired, leading to the development of hyperuricemia. We analyzed then whether improvement of muscle energy generation ameliorates exercise-induced puiine degradation. Glucose infusion or glucagon injection improves energy production in muscle glycogenosis type V. When a patient exercises under these treatments, the excess purine degradation and the development of hyperuricemia are abolished. On the other hand, no beneficial effect of these treatments was observed in glycogenosis type VII. Anaerobic contraction decreases ATP content in fast muscles of rats, while the degradation of adenine nucleotides is minimal in slow muscles. The threshold of "energy crisis" appears different between two muscle fiber types.
We conclude that myogenic hyperuricemia is a secondary hypemncemia caused by excess degmdadon of muscular adenine nucleotides. This type of hypennicemia seems common in genetic and acquired muscle-energy diseases.
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