| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
In vertebrates, the initial step in heme biosynthesis is the production of 5-aminolevulinic acid (ALA) by ALA synthase (ALAS). The ALAS1 gene encodes a ubiquitously expressed isozyme. Mice heterozygous null for ALAS1 (ALAS1+/-s) experience mitochondrial dysfunction (MD), impaired glucose tolerance (IGT) and insulin resistance (IR) past 20-weeks of age (aged-ALAS1+/-s). IGT/IR in aged-ALAS1+/-s was remedied by the oral administration of ALA for 1-week. By contrast, MD required 6-weeks of ALA-administration before improvements could be observed, indicating the IGT/IR phenotype is not due to MD. Aged-ALAS1+/-s showed impaired glycogen metabolism (IGyM) in skeletal muscle (SM)/liver and data indicate a defect in de novo glycogen synthesis that could account for the IGT/IR phenotype. Together, our data reveals an unexpected metabolic link between heme and glucose metabolism.
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