| Project/Area Number |
04454561
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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 |
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Principal Investigator |
KONO Norio Osaka Univ, Faculty of Medicine, Professor, 医学部, 教授 (30093412)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAJIMA Masamichi Osaka Univ, Faculty of Medicine, Assist Prof., 医学部, 講師 (00205262)
HANAFUSA Toshiaki Osaka Univ, Faculty of Medicine, Assist Prof., 医学部, 講師 (60164886)
NAMBA Mitsuyoshi Osaka Univ, Faculty of Medicine, Instructor, 医学部, 助手 (00183533)
NAKAJIMA Hiromu Osaka Univ, Faculty of Medicine, Instructor, 医学部, 助手 (50252680)
嶺尾 郁夫 大阪大学, 医学部, 助手 (40243240)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | Non-insulin-dependent diabetes mellitus / Glycolysis / Gluconeogenesis / Insulin action / Otsuka Long-Evans Tokushima Fatty rat / Phosphofructokinase / Promoter / Insulin resistance / OLETF / グルコキナーゼ / ピルビン酸キナーゼ / 糖尿病 / 遺伝子調節 / 遺伝子クローニング |
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| Research Abstract |
Phosphofructokinase (PFK) is a regulatory enzyme in glycolysis. Three isozymes are known as muscle (M), liver (L) and platelet (P) types. We compared human PFK-M and-L genes and various species M and L genes. The results suggest that the establishment of isozyme genes preceded the speciation of animal species during evolution.
Human PFK-M gene has tissue-specific two promoter system and slternative splicing mechanism. Similar promoter and expression system is evolutionally conserved in mouse PFK-M gene. Total PFK-M mRNA was decreased in cardiac and skeletal muscles of ketotic diabetic mice. This suggests that insulin regulates PFK-M gene expression at the level of transcription and/or splicing. Cultured islet cell tumor exhibited three isozyme mRNAs, being predominant L-type.
This indicates the significant role of PFK-L in the regulation of insulin secretion from pancreatic beta cells.
We disclosed two novel mutations in the PFK-M gene in Japanese patients with glycogenosis VII.There are three different mutations in three Japanese families, which is contrasted with a limited mumber of mutations common to the affected families in other racial population.
OLETF rats are animal model of insulin resistant diabetes. Increased activities and mRNA levels of both glycolytic and gluconeogenic regulatory enzymes in liver may be the reflection of expression of insulin resistance in the gluconeogenic enzymes. Defect of intracellular signal transduction of insulin or anti-insulin action of unidentified substance is possibly involved in the pathogenesis of insulin resistance in liver.
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