Response to Comment on Liu et al. Aberrant Expression of FBXO2 Disrupts Glucose Homeostasis Through Ubiquitin-Mediated Degradation of Insulin Receptor in Obese Mice. Diabetes 2017;66:689–698

Response to Comment on Liu et al. Aberrant Expression of FBXO2 Disrupts Glucose Homeostasis Through Ubiquitin-Mediated Degradation of Insulin Receptor in Obese Mice. Diabetes 2017;66:689–698


We appreciate Wong et al. (1) for their interest in our article (2). The specificity of an antibody could be affected by many factors including the detergents, blocking reagent, and incubating time and temperature as well as the quantity of secondary antibody. Wong et al. claimed that F-box only protein 2 (FBXO2) might not mediate glucose homeostasis in mice. Although the reason for this inconsistency is unclear, the animal models and feeding conditions were different in the two studies. In our study, to specifically explore the metabolic role of FBXO2 in the liver, adenovirus-mediated hepatic overexpression or knockdown was used. In contrast, Wong et al. used FBXO2 global knockout mice. As FBXO2 is widely expressed, the whole-body deletion of FBXO2 might differ from the liver-specific suppression of FBXO2. This phenomenon has been reported in many other studies. For example, severe insulin resistance was only observed in liver-specific insulin receptor (IR) knockout mice and not in skeletal muscle– or fat-specific IR knockout mice (3–5). In addition, TRB3 was shown to inhibit insulin signaling and promote insulin resistance in the liver (6–8). However, serum glucose or insulin levels, insulin sensitivity or glucose tolerance, and energy metabolism were not altered in genetic TRB3 deficient mice (9). Therefore, global TRB3 knockout mice displayed normal hepatic insulin signaling and glucose homeostasis (9). Thus, further studies are still needed to extensively investigate the metabolic role of FBXO2 in the liver under different physiological or pathophysiological conditions.

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Duality of Interest. No potential conflicts of interest relevant to this article were reported.



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