Fig. 9: ZFYVE28 is involved in insulin resistance and promotes phosphorylated insulin receptor degradation. | Nature Communications

Fig. 9: ZFYVE28 is involved in insulin resistance and promotes phosphorylated insulin receptor degradation.

From: ZFYVE28 mediates insulin resistance by promoting phosphorylated insulin receptor degradation via increasing late endosomes production

Fig. 9

A proposed model of the mechanism by which ZFYVE28 is involved in insulin signaling. ZFYVE28 is transcriptionally regulated by NOTCH1, which is inhibited by insulin through the RAS/ERK pathway. In obese noninsulin-resistant subjects, elevated insulin levels lead to enhanced inhibition of ZFYVE28, thereby causing decreased ZFYVE28 expression. However, in insulin-resistant MetS subjects, insulin signaling is impaired and the inhibitory effect on ZFYVE28 is diminished; thus, ZFYVE28 expression is upregulated. Furthermore, ZFYVE28 colocalizes with early endosomes via its FYVE domain, inhibits the conversion of early endosomes to recycling endosomes but promotes the conversion to late endosomes, ultimately promoting the degradation of phosphorylated insulin receptor which is endocytosed into early endosomes.

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