Rab10 and Brown Adipose Tissue
We’ve generated an adipose-specific Rab10 knockout mouse (AdipoCre-Rab10 KO). The phenotype of Rab10 KO primary adipocytes -- 50% blunting of Glut4 translocation and a corresponding inhibition of insulin-stimulated glucose uptake -- is identical to the phenotype of cultured adipocytes in which Rab10 has been knocked-down, establishing that insulin signals to Glut4 by both Rab10-dependent and -independent mechanism, and that both are required for the full effect of insulin on Glut4 translocation to the PM. AdipoCre-Rab10 KO mice develop an insulin resistance due to a reduced liver sensitivity to insulin.
To further understand the mechanisms underlying this effect and because Brown Adipose Tissue (BAT) has recently gained attention for its metabolic role, we generated UCP1-Cre-Rab10 KO mice. Knocking out Rab10 in the BAT was sufficient to induce whole body glucose intolerance an insulin resistant, with no impact on thermogenesis. These results further indicate the prominent role of BAT in glucose homeostasis.