| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
Few studies have interrogated the mechanisms of β-cell dysfunction at the level of mRNA translation under conditions of high fat diet (HFD) consumption. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed global reductions in mRNA translation with a reduction in the polyribosome/monoribosome ratio. HFD-islets demonstrated evidence of oxidative stress and DNA damage, as well as activation of p53. MIN-6 β-cells treated with doxorubicin to directly induce DNA damage mimicked our observed effects in islets. Islets from animals treated with pioglitazone demonstrated a reversal of effects observed from HFD. Finally, HFD-islets demonstrated reduced expression of ribosome biogenesis genes and the key translation initiation factor eIF4E. We propose an effect of chronic HFD on β-cells, wherein DNA damage owing to oxidative stress results in p53 activation and a resultant inhibition of mRNA translation.
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