Figure 10: Model for MARCH1-mediated regulation of insulin action.
From: MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels
In the basal state, MARCH1 ubiquitinates and degrades INSRβ; thereby reducing surface INSR expression. In the insulin-sensitive state, INSR activation inhibits FOXO1, resulting in transcriptional repression of MARCH1, increased surface INSR levels, and preserved insulin signalling. In the insulin-resistant state, insulin fails to inhibit FOXO1, resulting in inappropriately increased MARCH1 expression, decreased surface INSR levels, and impaired insulin signalling.
