Molecular identification and characterization of a novel nuclear protein whose expression is up-regulated in insulin-resistant animals.

Energy metabolism is the most fundamental capacity for mammals, impairment of which causes a variety of diseases such as type 2 diabetes and insulin resistance. Here, we identified a novel gene, termed diabetes-related ankyrin repeat protein that is up-regulated in the heart of KKA(y) mouse, a type 2 diabetes and insulin resistance model animal. contains putative nuclear localization signals and four tandem ankyrin-like repeats. Its expression is restricted in heart, skeletal muscle, and brown adipose. Western blot analysis and immunocytochemistry of Chinese hamster ovary (CHO) and COS-7 cells reveal that Dduanyu37 is a nuclear protein. When Dduanyu37 is expressed in CHO cells, [1-(14)C]palmitate uptake is significantly decreased, whereas the palmitate oxidation does not show significant change. Furthermore, Dduanyu37 expression is altered by the change of energy supply induced by excess fatty acid treatment of skeletal myotube in vitro and fasting treatment of C57 mouse in vivo. We confirmed that Dduanyu37 expression is also altered in Zucker fatty rat, another insulin resistance model animal. Taken together, these data suggest that Dduanyu37 is a novel nuclear protein potentially involved in the energy metabolism. Detailed analysis of Dduanyu37 may provide new insights in the energy metabolism.

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