In support of decreased skeletal-muscle-specific glucose uptake, immunofluorescent staining of skeletal muscle tissues of insulin-injected animals revealed a disrupted GLUT4 membrane integration with membrane-proximal accumulation of GLUT4 vesicles in Exoc5-SMKO male and female mice compared with littermate controls (Fig. 4I) These results indicate that impaired glucose tolerance and insulin resistance in male Exoc5-SMKO mice were mostly due to decreases in insulin-stimulated glucose uptake in skeletal muscle. This evidence concerns the gene INS and Insulin resistance.