Tumor suppressor F-box and WD repeat domain-containing 7 (FBW7), an E3 ubiquitin-ligase, also plays important roles in the regulation of metabolism. However, the contribution of FBW7 on β-cells remains largely unknown. Our study indicated that the expression of FBW7 in pancreatic β-cells was significantly higher than that in exocrine cells. The expression of FBW7 in β- cells from high-fat diet (HFD) fed mice significantly decreased than chow diet fed mice. Similarly, the expression of FBW7 in β-cells from db/db mice were also decreased. The reduced expression of FBW7 in β-cells from these animal models accompanied with the elevated expression of dedifferentiation marker ALDH1A3. In vitro study suggested that overexpression of FBW7 suppressed expression of ALDH1A3 protein levels, but not mRNA levels, in MIN6 β-cells. We also found that FBW7 regulated ALDH1A3 stability by promoting its ubiquitination and degradation. Bioinformatic analysis revealed the conserved sequence in ALDH1A3 protein as the potential FBW7 substrates. Together, our study suggested that FBW7 may play important role in the regulation of β-cell dedifferentiation via its novel substrate ALDH1A3.

Disclosure

J. Xu: None. X. Li: None.

© 2019 by the American Diabetes Association.
2019
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